Composition for treating ringworm

Abstract

Provided is a novel composition for treating ringworm.　This composition for treating ringworm contains at least one selected from the group consisting of a bacterial strain of Staphylococcus hominis, a bacterial strain of Staphylococcus haemolyticus, and a bacterial strain of Staphylococcus warneri.

Description

Composition for treating tinea

[0001] The present invention relates to a composition for treating tinea.

[0002] Tinea pedis is a skin infection caused by the fungus Trichophyton (also known as tinea fungus). Depending on the site of onset, tinea pedis is classified as tinea pedis (athlete's foot), tinea unguium (tinea unguium), tinea manubriata (athlete's foot), tinea corporis (ringworm), tinea cruris (jock itch), and tinea capitis.

[0003] Tinea is transmitted by Trichophyton fungi that are present in patients with tinea. For example, it is known that the main route of infection for the common conditions tinea pedis (athlete's foot) and tinea unguium (tinea unguium) is Trichophyton that is present in swimming pools, public baths, restaurants, slippers, etc.

[0004] Tinea fungus is a non-resident fungus that parasitizes the stratum corneum and subcutaneous tissue of the skin. When it multiplies and invades the stratum corneum, inflammation and blisters occur, causing symptoms such as itching. Tinea fungus feeds on keratin, the main component of keratin.

[0005] Antifungal drugs such as itraconazole, miconazole, clotrimazole, ketoconazole, bifonazole, lanoconazole, luliconazole, efinaconazole, fosravuconazole, terbinafine, and butenafine have been used to treat tinea.

[0006] For example, Non-Patent Document 1 describes that prepubertal children frequently develop tinea corporis and tinea capitis, while adolescents and adults frequently develop tinea corporis, tinea cruris (jock itch), and tinea pedis (athlete's foot); that because there are diseases that show similar clinical symptoms, it may be preferable to make a diagnosis using potassium hydroxide preparations or culture; and that creams or oral medications should be selected as appropriate for treatment.

[0007] Furthermore, Patent Document 1 describes an invention relating to an external preparation for treating onychomycosis, which contains a) an antifungal active substance, b) a volatile component, c) a medium-chain fatty acid triglyceride, and d) ethyl lactate. It is stated that the external preparation described in Patent Document 1 has excellent properties in terms of nail permeability, medicinal efficacy, and formulation properties by using a medium-chain fatty acid triglyceride as a non-volatile component and ethyl lactate as a permeation enhancer.

[0008] Patent Document 1 describes that topical preparations used to treat onychomycosis are superior to oral preparations in that they have fewer systemic side effects and fewer drug-drug interactions.

[0009] International Publication No. 2019 / 088005

[0010] American Family Physician, Volume 90, Number 10, 702-711.

[0011] In this situation, further development of drugs for treating tinea is underway.

[0012] The present invention provides, for example, the following compositions for treating tinea.

[0013] [1] A composition for treating tinea, comprising at least one selected from the group consisting of a strain of Staphylococcus hominis, a strain of Staphylococcus haemolyticus, and a strain of Staphylococcus warneri. [2] The composition for treating tinea described in [1] above, comprising a strain of Staphylococcus hominis. [3] The composition for treating tinea described in [2] above, wherein the strain of Staphylococcus hominis has a 16s rDNA containing the nucleotide sequence of SEQ ID NO: 1 or a 16s rDNA containing a nucleotide sequence having 95% or more identity to SEQ ID NO: 1, and has an anti-tinea activity. [4] The composition for treating tinea according to [2] or [3] above, wherein the Staphylococcus hominis strain comprises at least one selected from the group consisting of Staphylococcus hominis ATCC27844, Staphylococcus hominis ATCC27845, Staphylococcus hominis ATCC700236, and Staphylococcus hominis A9 (ATCC Accession No. PTA-125203). [5] The composition for treating tinea according to any of [1] to [4] above, wherein the Staphylococcus haemolyticus strain has a 16s rDNA comprising the nucleotide sequence of SEQ ID NO: 10 or a 16s rDNA comprising a nucleotide sequence having 95% or more identity to SEQ ID NO: 10, and has an anti-tinea activity. [7] The composition for treating tinea according to [5] or [6] above, wherein the Staphylococcus haemolyticus strain comprises at least one selected from the group consisting of Staphylococcus haemolyticus ATCC 29970, Staphylococcus haemolyticus ATCC 700564, and Staphylococcus haemolyticus ATCC 29969. [8] The composition for treating tinea according to any of [1] to [7] above, wherein the Staphylococcus haemolyticus strain comprises a Staphylococcus warneri strain.[9] The composition for treating tinea according to [8] above, wherein the Staphylococcus warneri strain has a 16s rDNA containing the nucleotide sequence of SEQ ID NO: 17 or a 16s rDNA containing a nucleotide sequence having 95% or more identity to SEQ ID NO: 17, and has anti-tinea activity.

[10] The composition for treating tinea according to [8] or [9] above, wherein the Staphylococcus warneri strain comprises Staphylococcus warneri ATCC27836.

[11] The composition for treating tinea according to any of [1] to

[10] above, wherein the causative fungus of tinea comprises a fungus of the genus Trichophyton.

[12] The composition for treating tinea according to

[11] above, wherein the causative fungus of tinea comprises at least one fungus selected from the group consisting of a fungus strain of Trichophyton rubrum, a fungus strain of Trichophyton mentagrophytes, and a fungus strain of Trichophyton tonsurans.

[13] The composition for treating tinea according to any one of [1] to

[12] above, which is an external preparation.

[14] A method for producing a composition for treating tinea, comprising: (1) a step of collecting and culturing a bacterial flora from at least one of a human ankle and a human sole, (2) a step of isolating and culturing the cultured bacterial flora to obtain a candidate bacterium, (3) a step of evaluating the anti-tinea fungal activity of the candidate bacterium to identify a bacterium having anti-tinea fungal activity, and (4) a step of preparing a composition for treating tinea, which comprises the bacterium having anti-tinea fungal activity, wherein the bacterium having anti-tinea fungal activity comprises at least one selected from the group consisting of a strain of Staphylococcus hominis, a strain of Staphylococcus haemolyticus, and a strain of Staphylococcus warneri.

[0014] The present invention provides a novel composition for treating tinea. In a preferred embodiment, the composition can be used in cases where artificial chemical synthesis and extraction of a medicinal compound are difficult or where the medicinal effect is based on a vital reaction derived from live bacteria, and can have one or more of the following effects: prevention or reduction of side effects, prevention or suppression of skin rash around the affected area, high skin adhesion, maintenance of remission, prevention of recurrence, reduction in the number of administrations, improvement of compliance, and high therapeutic effect.

[0015]

[0023] Figure 1 shows typical examples of evaluations of anti-tinea fungal activity. Figure 2 shows the results of anti-tinea fungal activity for each species of candidate fungus (91 strains) obtained from the ankle and sole. Figure 3 shows a phylogenetic tree of known and candidate fungi of the genus Staphylococcus. Figure 4 shows a phylogenetic tree of known and candidate fungi of Staphylococcus hominis. Figure 5 shows a phylogenetic tree of known and candidate fungi of Staphylococcus haemolyticus.

[0016] The present invention will be described in detail below.

[0017] <Composition for treating tinea> The composition for treating tinea according to the present invention contains at least one strain selected from the group consisting of a strain of Staphylococcus hominis, a strain of Staphylococcus haemolyticus, and a strain of Staphylococcus warneri. The composition for treating tinea according to the present invention can treat tinea. In this specification, "treatment" means preventing or inhibiting the growth of Trichophyton fungi (so-called tinea fungi), killing them, or bacteriostasizing them.

[0018] It is known that the onset and recurrence of tinea varies from person to person. The present inventors predicted that this individual difference is due to the resident skin flora, and investigated the effects of resident skin flora collected from the ankles and soles of healthy individuals and known strains of Staphylococcus on tinea fungi. As a result, they found that strains of Staphylococcus hominis (hereinafter also referred to as "S. hominis"), Staphylococcus haemolyticus (hereinafter also referred to as "S. haemolyticus"), and Staphylococcus warneri (hereinafter also referred to as "S. warneri"), which are resident skin flora, are effective in treating tinea. According to the present invention, a novel composition for treating tinea can be provided.

[0019] Furthermore, because S. hominis, S. haemolyticus, and S. warneri strains are normal skin flora, they have few or no side effects, and therefore may be effective in preventing or suppressing skin rash around the affected area that can occur with conventional topical preparations.

[0020] Furthermore, because S. hominis, S. haemolyticus, and S. warneri strains are naturally occurring bacteria on the skin, they tend to colonize the skin, which can result in longer-lasting effects on affected areas of the skin and reduced administration frequency compared to conventional topical preparations.

[0021] Furthermore, because S. hominis strains, S. haemolyticus strains, and S. warneri strains are live bacteria that are normally present on the skin, they may have therapeutic effects even when it is difficult to artificially chemically synthesize or extract medicinal compounds, or when the medicinal effects are based on vital reactions derived from live bacteria.

[0022] Therefore, the composition for treating tinea according to the present invention can have advantages such as fewer side effects, better compliance, and higher efficacy compared to conventional topical preparations.

[0023] Staphylococcus hominis Strains In one embodiment, the composition for treating ringworm comprises a strain of Staphylococcus hominis.

[0024] Staphylococcus hominis strains are coagulase-negative staphylococci (CNS) and gram-positive bacteria. S. hominis strains are normal skin flora. It is presumed that S. hominis strains prevent or inhibit the growth and colonization of tinea fungi, kill them, or act as a bacteriostat by directly or indirectly interfering with them or competing for habitat.

[0025] The S. hominis strain preferably includes an S. hominis strain having anti-trichophyton activity. That is, in a preferred embodiment, a composition for treating tinea is provided that includes an S. hominis strain having anti-trichophyton activity. In this specification, "antitrinobacterial activity" means that when the anti-trichophyton activity is evaluated by the method described in "4. Evaluation of anti-trichophyton activity" in the Examples, the evaluation result is "++" or "+", preferably "++". Therefore, S. hominis strains having anti-trichophyton activity can treat tinea.

[0026] Although not particularly limited, S. hominis strains preferably have a 16s rDNA containing the nucleotide sequence of SEQ ID NO: 1 or a 16s rDNA containing a nucleotide sequence with 95% or greater identity to SEQ ID NO: 1 and have anti-tinea activity. As shown in the Examples, SEQ ID NO: 1 is the nucleotide sequence of the region flanked by two consensus sequences shared by 16s rDNAs of the genus Staphylococcus. Of the two consensus sequences, the 5'-side consensus sequence is consensus sequence 1 (AGCTTGC), and the 3'-side consensus sequence is consensus sequence 2 (AAGCTGG), both of which are included in SEQ ID NO: 1. Here, for example, "16s rDNA containing the nucleotide sequence of SEQ ID NO: 1" means that the 16s rDNA contains the nucleotide sequence of SEQ ID NO: 1. In this specification, the nucleotide sequences of SEQ ID NOs: 1 to 18 are identified by the method described in the Examples. Furthermore, if a given bacterium has two or more types of 16s rDNA, the most abundant 16s rDNA is defined as the 16s rDNA of that bacterium. If two or more types of 16s rDNA are present in equal numbers, the 16s rDNA with the most identical base sequence to SEQ ID NO: 1 for S. hominis strains, SEQ ID NO: 10 for S. haemolyticus strains, and SEQ ID NO: 17 for S. warneri strains is defined as the 16s rDNA of that bacterium.

[0027] A base sequence having 95% or more identity to SEQ ID NO: 1 preferably has 96% or more, 96.5% or more, 97% or more, 97.5% or more, 98% or more, 98.1% or more, 98.2% or more, 98.3% or more, 98.4% or more, 98.5% or more, 98.6% or more, 98.7% or more, 98.8% or more, 98.9% or more, 99% or more, 99.1% or more, 99.2% or more, 99.3% or more, 99.4% or more, 99.5% or more, 99.6% or more, 99.7% or more, 99.8% or more, or 99.9% or more identity to SEQ ID NO: 1.

[0028] Mutations in a nucleotide sequence having 95% or more identity to SEQ ID NO: 1 include substitutions, deletions, insertions, additions, and combinations thereof. In a preferred embodiment, the number of substitutions, deletions, insertions, additions, and combinations thereof is preferably 1 to 10, more preferably 1 to 5, and even more preferably 1 to 2.

[0029] The substitution is not particularly limited, but is preferably at least one substitution selected from the group consisting of guanine at position 45, thymine at position 139, thymine at position 140, adenine at position 309, and cytosine at position 1265 of SEQ ID NO: 1. In one embodiment, guanine at position 45 of SEQ ID NO: 1 may be substituted with adenine (45G>A (also written as G45A)), thymine at position 139 with cytosine (139T>C), thymine at position 140 with cytosine (140T>C), adenine at position 309 with cytosine (309A>C), and cytosine at position 1265 with thymine (1265C>T).

[0030] The deletion is not particularly limited, but may include deletion of adenine at position 488 of SEQ ID NO: 1 (488delA (also denoted as A488Δ)).

[0031] The insertion is not particularly limited, and may be inserted between positions 1182 and 1183 and between positions 1235 and 1236 of SEQ ID NO: 1. In one embodiment, an adenine (1182_1183insA (also represented as Δ1183A)) may be inserted between positions 1182 and 1183 of SEQ ID NO: 1, and a guanine (1235_1236insG) may be inserted between positions 1235 and 1236.

[0032] Furthermore, the base sequence having 95% or more identity to SEQ ID NO: 1 may be one possessed by a S. hominis strain as a result of natural mutation or the like, or may be one obtained by artificial mutation treatment. Examples of artificial mutation treatment include methods such as genetic engineering, genome editing, ultraviolet irradiation, radiation irradiation, ethyl methanesulfonate (MES) treatment, N-methyl-N-nitrosoguanidine (NTG) treatment, and nitrous acid treatment. These mutation treatments may be used alone or in combination of two or more types.

[0033] Examples of base sequences having 95% or more identity with SEQ ID NO: 1 include SEQ ID NOs: 2 to 9. The mutation sites of SEQ ID NOs: 2 to 9 are shown in Table 1 below.

[0034]

[0035] Examples of S. hominis strains having 16s rDNA containing the base sequence of SEQ ID NO: 1 include, but are not limited to, S. hominis ATCC27844, S. hominis ATCC27845, and the like.

[0036] Examples of S. hominis strains having 16s rDNA containing a base sequence with 95% or more identity to SEQ ID NO: 1 and having anti-tinea activity include, but are not limited to, S. hominis ATCC700236 and S. hominis A9 (ATCC accession number: PTA-125203).

[0037] In one embodiment, examples of S. hominis strains include, but are not limited to, Staphylococcus hominis ATCC27844, Staphylococcus hominis ATCC27845, Staphylococcus hominis ATCC700236, Staphylococcus hominis FDAARGOS_748, Staphylococcus hominis J6, Staphylococcus hominis FDAARGOS_136, Staphylococcus hominis A9 (ATCC Accession No. PTA-125203), Staphylococcus hominis C2, Staphylococcus hominis AMT2, Staphylococcus hominis AMT3, Staphylococcus hominis AMT4-C2, Staphylococcus hominis AMT4-G1, and Staphylococcus hominis. In addition to the above, strains belonging to S. hominis that can be used include those listed in "NCBI," [online], archived February 17, 2022, [searched February 17, 2022], and the Internet at <https: / / www.ncbi.nlm.nih.gov / genome / browse / #! / prokaryotes / 2014 / >. Among these, the strains belonging to S. hominis preferably include at least one selected from the group consisting of S. hominis ATCC27844, S. hominis ATCC27845, S. hominis ATCC700236, S. hominis FDAARGOS_748, S. hominis J6, S. hominis FDAARGOS_136, and S. hominis A9, and more preferably include at least one selected from the group consisting of S. hominis ATCC27844, S. hominis ATCC27845, S. hominis ATCC700236, and S. hominis A9. The above-mentioned strains belonging to S. hominis may be used alone or in combination of two or more.

[0038] Anti-trichophyton strains of S. hominis can be easily prepared by the following method. Specifically, the method for preparing anti-trichophyton strains of S. hominis includes the steps of (1) collecting and culturing bacterial flora from at least one of the ankle and sole of a human (preferably a healthy individual without tinea symptoms), (2) isolating and culturing the cultured bacterial flora to obtain candidate bacteria, and (3) evaluating the anti-trichophyton activity of the candidate bacteria to identify bacteria with anti-trichophyton activity. Each step is described below. The bacterial flora of the human ankle and sole typically includes strains of S. hominis, which are known as normal skin flora. According to the above method, anti-trichophyton strains of S. hominis can be easily prepared.

[0039] The concentration of the S. hominis strain in the composition for treating ringworm is 10 ３ ~10 １１ CFU / g, preferably 10 ４ ~10 １０ More preferably, 10 CFU / g ５ ~10 ９ It is more preferable that the concentration is CFU / g. In this specification, "CFU" means colony forming unit. In this specification, the concentration (CFU / g) of the bacterial strain in the composition for treating tinea is calculated by diluting the composition for treating tinea to an appropriate concentration, smearing it on an agar medium for bacterial culture, and counting the colonies that appear after culture (see Clinical Microbiology Procedures Handbook volume 2 THIRD EDITION).

[0040] The form of the S. hominis strain in the composition for treating tinea is not particularly limited, but is preferably in the form of a dry powder (for example, freeze-dried or spray-dried).

[0041] Staphylococcus haemolyticus Strains In one embodiment, the composition for treating ringworm comprises a strain of Staphylococcus haemolyticus.

[0042] Staphylococcus haemolyticus strains are coagulase-negative staphylococci (CNS) and gram-positive bacteria. S. haemolyticus strains are normal skin flora. It is presumed that S. haemolyticus strains also prevent or inhibit the growth of tinea fungi, kill tinea fungi, or act as bacteriostatic agents by directly or indirectly interfering with the fungus or competing for habitat.

[0043] The S. haemolyticus strain preferably includes an S. haemolyticus strain having anti-trichophytic activity. That is, in one preferred embodiment, a composition for treating tinea is provided, which includes an S. haemolyticus strain having anti-trichophytic activity. The S. haemolyticus strain having anti-trichophytic activity can treat tinea.

[0044] The S. haemolyticus strain is not particularly limited, but is preferably one having a 16s rDNA containing the nucleotide sequence of SEQ ID NO: 10 or a 16s rDNA containing a nucleotide sequence with 95% or more identity to SEQ ID NO: 10 and having anti-tinea activity. As shown in the Examples, SEQ ID NO: 10 is the nucleotide sequence of the region flanked by two consensus sequences shared by 16s rDNAs of the genus Staphylococcus. Of the two consensus sequences, the consensus sequence on the 5' side is consensus sequence 1 (AGCTTGC), and the consensus sequence on the 3' side is consensus sequence 2 (AAGCTGG), both of which are included in SEQ ID NO: 10. Here, for example, "16s rDNA containing the nucleotide sequence of SEQ ID NO: 10" means that the nucleotide sequence of SEQ ID NO: 10 is contained in the nucleotide sequence of the 16s rDNA.

[0045] A base sequence having 95% or more identity to SEQ ID NO: 10 preferably has 96% or more, 96.5% or more, 97% or more, 97.5% or more, 98% or more, 98.1% or more, 98.2% or more, 98.3% or more, 98.4% or more, 98.5% or more, 98.6% or more, 98.7% or more, 98.8% or more, 98.9% or more, 99% or more, 99.1% or more, 99.2% or more, 99.3% or more, 99.4% or more, 99.5% or more, 99.6% or more, 99.7% or more, 99.8% or more, or 99.9% or more identity to SEQ ID NO: 10.

[0046] Mutations in a nucleotide sequence having 95% or more identity to SEQ ID NO: 10 include substitutions, deletions, insertions, additions, and combinations thereof. In a preferred embodiment, the number of substitutions, deletions, insertions, additions, and combinations thereof is preferably 1 to 10, more preferably 1 to 5, and even more preferably 1 to 2.

[0047] The substitution is not particularly limited, but is preferably at least one selected from the group consisting of cytosine at position 96, guanine at position 109, adenine at position 398, cytosine at position 952, and cytosine at position 1186 of SEQ ID NO: 10. In one embodiment, the cytosine at position 96 of SEQ ID NO: 10 can be substituted with thymine (96C>T), the guanine at position 109 with adenine (109G>A), the adenine at position 398 with guanine (398A>G), the cytosine at position 952 with thymine (952C>T), or the cytosine at position 1186 with thymine (1186C>T).

[0048] The deletion is not particularly limited, and may include deletion of adenine at position 1210 (1210delA), adenine at position 1219 (1219delA), thymine at position 1225 (1225delT), or adenine at position 1263 (1263delA) of SEQ ID NO: 10.

[0049] The insertion is not particularly limited, and may be between positions 1117 and 1118, between positions 1195 and 1196, or between positions 1234 and 1235 of SEQ ID NO: 10. In one embodiment, a guanine (1117_1118insG) may be inserted between positions 1117 and 1118 of SEQ ID NO: 10, a cytosine (1195_1196insC) may be inserted between positions 1195 and 1196, or a guanine (1234_1235insG) may be inserted between positions 1234 and 1235.

[0050] The base sequence having 95% or more identity to SEQ ID NO: 10 may be one possessed by other S. haemolyticus strains as a result of natural mutation or the like, as with S. hominis strains, or may be one obtained by artificial mutation treatment. Examples of artificial mutation treatment include genetic engineering, genome editing, ultraviolet irradiation, radiation irradiation, ethyl methanesulfonate (MES) treatment, N-methyl-N-nitrosoguanidine (NTG) treatment, and nitrous acid treatment. These mutation treatments may be used alone or in combination of two or more types.

[0051] Examples of base sequences having 95% or more identity with SEQ ID NO: 10 include SEQ ID NOs: 11 to 16. The mutation sites in SEQ ID NOs: 11 to 16 are shown in Table 2 below.

[0052]

[0053] Examples of S. haemolyticus strains having 16s rDNA containing the base sequence of SEQ ID NO: 10 include, but are not limited to, S. haemolyticus ATCC29970, S. haemolyticus ATCC700564, and the like.

[0054] In one embodiment, the S. haemolyticus strain is not particularly limited, but examples include Staphylococcus haemolyticus ATCC29970, Staphylococcus haemolyticus ATCC700564, Staphylococcus haemolyticus ATCC29969, Staphylococcus haemolyticus SH_12, and Staphylococcus haemolyticus JCSC1435. In addition to the above, S. haemolyticus strains that can be used include those listed in "NCBI," [online], archived February 17, 2022, [searched February 17, 2022], and on the Internet at <https: / / www.ncbi.nlm.nih.gov / genome / browse / #! / prokaryotes / 1141 / >. Of these, the S. haemolyticus strain preferably includes at least one selected from the group consisting of S. haemolyticus ATCC29970, S. haemolyticus ATCC700564, S. haemolyticus ATCC29969, S. haemolyticus SH_12, and S. haemolyticus JCSC1435, and more preferably includes at least one selected from the group consisting of Staphylococcus haemolyticus ATCC29970, Staphylococcus haemolyticus ATCC700564, and Staphylococcus haemolyticus ATCC29969. The above-mentioned S. haemolyticus strains may be used alone or in combination of two or more.

[0055] Like S. hominis strains, S. haemolyticus strains with anti-trichophytic activity can be easily prepared by the following method. Specifically, the method for preparing S. haemolyticus strains with anti-trichophytic activity includes the steps of (1) collecting and culturing bacterial flora from at least one of the ankle and sole of a human (preferably a healthy individual without tinea symptoms), (2) isolating and culturing the cultured bacterial flora to obtain candidate bacteria, and (3) evaluating the anti-trichophytic activity of the candidate bacteria to identify bacteria with anti-trichophytic activity. S. haemolyticus strains with anti-trichophytic activity can also be contained in the bacterial flora of the human ankle and sole. Therefore, according to the above method, S. haemolyticus strains with anti-trichophytic activity can be easily prepared.

[0056] The concentration of the S. haemolyticus strain in the composition for treating ringworm is 10 ３ ~10 １１ CFU / g, preferably 10 ４ ~10 １０ More preferably, 10 CFU / g ５ ~10 ９ More preferably, it is CFU / g.

[0057] The form of the S. haemolyticus strain in the composition for treating tinea is not particularly limited, but is preferably in the form of a dry powder (for example, freeze-dried or spray-dried).

[0058] Staphylococcus warneri In one embodiment, the composition for treating ringworm comprises a strain of Staphylococcus warneri.

[0059] Staphylococcus warneri strains are coagulase-negative staphylococci (CNS) and gram-positive bacteria. S. warneri strains are normal skin flora. It is presumed that S. warneri strains also prevent or inhibit the growth of tinea fungi, kill tinea fungi, or act as bacteriostatic agents by directly or indirectly interfering with the fungus or competing for habitat.

[0060] The S. warneri strain preferably includes an S. warneri strain having anti-trichophytic activity. That is, in one preferred embodiment, a composition for treating tinea is provided, which includes an S. warneri strain having anti-trichophytic activity. The S. warneri strain having anti-trichophytic activity can treat tinea.

[0061] The S. warneri strain is not particularly limited, but is preferably one having a 16s rDNA containing the nucleotide sequence of SEQ ID NO: 17 or a 16s rDNA containing a nucleotide sequence with 95% or greater identity to SEQ ID NO: 17 and having anti-tinea activity. As shown in the Examples, SEQ ID NO: 17 is the nucleotide sequence of the region flanked by two consensus sequences shared by 16s rDNAs of the genus Staphylococcus. Of the two consensus sequences, the consensus sequence on the 5' side is consensus sequence 1 (AGCTTGC), and the consensus sequence on the 3' side is consensus sequence 2 (AAGCTGG), both of which are included in SEQ ID NO: 17. Here, for example, "16s rDNA containing the nucleotide sequence of SEQ ID NO: 17" means that the nucleotide sequence of SEQ ID NO: 17 is contained in the 16s rDNA.

[0062] A base sequence having 95% or more identity to SEQ ID NO: 17 preferably has 96% or more, 96.5% or more, 97% or more, 97.5% or more, 98% or more, 98.1% or more, 98.2% or more, 98.3% or more, 98.4% or more, 98.5% or more, 98.6% or more, 98.7% or more, 98.8% or more, 98.9% or more, 99% or more, 99.1% or more, 99.2% or more, 99.3% or more, 99.4% or more, 99.5% or more, 99.6% or more, 99.7% or more, 99.8% or more, or 99.9% or more identity to SEQ ID NO: 17.

[0063] Mutations in a nucleotide sequence having 95% or more identity to SEQ ID NO: 17 include substitutions, deletions, insertions, additions, and combinations thereof. In a preferred embodiment, the number of substitutions, deletions, insertions, additions, and combinations thereof is preferably 1 to 10, more preferably 1 to 5, and even more preferably 1 to 2.

[0064] The substitution is not particularly limited, but is preferably a cytosine at position 52 of SEQ ID NO: 17. In one embodiment, the cytosine at position 52 of SEQ ID NO: 17 may be substituted with a guanine (52C>G).

[0065] The base sequence having 95% or more identity to SEQ ID NO: 17 may be one possessed by other S. warneri strains as a result of natural mutation or the like, as with S. hominis strains, or may be one obtained by artificial mutation treatment. Examples of artificial mutation treatment include genetic engineering, genome editing, ultraviolet irradiation, radiation irradiation, ethyl methanesulfonate (MES) treatment, N-methyl-N-nitrosoguanidine (NTG) treatment, and nitrous acid treatment. These mutation treatments may be used alone or in combination of two or more.

[0066] An example of a base sequence having 95% or more identity with SEQ ID NO: 17 is SEQ ID NO: 18. The mutation sites in SEQ ID NO: 18 are shown in Table 3 below.

[0067]

[0068] Examples of S. warneri strains having 16s rDNA containing the base sequence of SEQ ID NO: 17 include, but are not limited to, S. warneri ATCC27836.

[0069] In one embodiment, S. warneri strains include, but are not limited to, S. warneri ATCC27836, S. warneri NCTC7291, S. warneri WB224, S. warneri 16A, S. warneri 22.1, etc. In addition to the above, S. warneri strains that can be used include those listed in "NCBI," [online], archived February 17, 2022, [retrieved February 17, 2022], and the Internet at https: / / www.ncbi.nlm.nih.gov / genome / browse / #! / prokaryotes / 2073 / . Of these, the S. warneri strain preferably includes at least one selected from the group consisting of Staphylococcus warneri ATCC27836, S. warneri NCTC7291, S. warneri WB224, S. warneri 16A, S. warneri 22.1, and S. warneri WS479, and more preferably includes S. warneri ATCC 27836. The above-mentioned S. warneri strains may be used alone or in combination of two or more.

[0070] Like S. hominis strains, S. warneri strains with anti-trichophytic activity can be easily prepared by the following method. Specifically, the method for preparing S. warneri strains with anti-trichophytic activity includes the steps of (1) collecting and culturing bacterial flora from at least one of the ankle and sole of a human (preferably a healthy individual without tinea symptoms), (2) isolating and culturing the cultured bacterial flora to obtain candidate bacteria, and (3) evaluating the anti-trichophytic activity of the candidate bacteria to identify bacteria with anti-trichophytic activity. S. warneri strains with anti-trichophytic activity can also be contained in the bacterial flora of the human ankle and sole. Therefore, according to the above method, S. warneri strains with anti-trichophytic activity can be easily prepared.

[0071] The concentration of the S. warneri strain in the composition for treating ringworm is 10 ３ ~10 １１ CFU / g, preferably 10 ４ ~10 １０ More preferably, 10 CFU / g ５ ~10 ９ More preferably, it is CFU / g.

[0072] The form of the S. warneri strain in the composition for treating tinea is not particularly limited, but is preferably in the form of a dry powder (for example, freeze-dried or spray-dried).

[0073] [Other Staphylococcus Strains] The composition for treating ringworm may further contain other Staphylococcus strains. Here, "other Staphylococcus strains" refers to Staphylococcus strains other than S. hominis, S. haemolyticus, and S. warneri.

[0074] Other strains of the genus Staphylococcus include, but are not limited to, species that have been reported to be isolated from humans, such as Staphylococcus saprophyticus strains, Staphylococcus kloosii strains, Staphylococcus lugdunensis strains, Staphylococcus capitis strains, Staphylococcus caprae strains, Staphylococcus epidermidis strains, and Staphylococcus aureus strains.

[0075] Examples of S. saprophyticus strains include those listed in "NCBI," [online], archived February 17, 2022, [searched February 17, 2022], and the internet: <https: / / www.ncbi.nlm.nih.gov / genome / browse / #! / prokaryotes / 1350 / >. Examples of S. kloosii strains include those listed in "NCBI," [online], archived February 17, 2022, [searched February 17, 2022], and the internet: <https: / / www.ncbi.nlm.nih.gov / genome / browse / #! / prokaryotes / 66884 / >. Examples of S. lugdunensis strains include those listed in "NCBI", [online], archived February 17, 2022, [searched February 17, 2022], and the internet: <https: / / www.ncbi.nlm.nih.gov / genome / browse / #! / prokaryotes / 2548 / >. Examples of S. capitis strains include those listed in "NCBI", [online], archived February 17, 2022, [searched February 17, 2022], and the internet: <https: / / www.ncbi.nlm.nih.gov / genome / browse / #! / prokaryotes / 2054 / >. Examples of S. caprae strains include those listed in "NCBI," [online], archived February 17, 2022, [searched February 17, 2022], and the internet: <https: / / www.ncbi.nlm.nih.gov / genome / browse / #! / prokaryotes / 1971 / >. Examples of S. epidermidis (Staphylococcus epidermidis) strains include those listed in "NCBI," [online], archived February 17, 2022, [searched February 17, 2022], and the internet: <https: / / www.ncbi.nlm.nih.gov / genome / browse / #! / prokaryotes / 155 / >.Examples of S. aureus strains include those listed in NCBI, [online], archived February 17, 2022, [retrieved February 17, 2022], internet: https: / / www.ncbi.nlm.nih.gov / genome / browse / #! / prokaryotes / 154 / .

[0076] From the viewpoint of achieving a higher therapeutic effect against tinea, the other Staphylococcus strains preferably include at least one selected from the group consisting of S. capitis, S. caprae, S. epidermidis (Staphylococcus epidermidis), Staphylococcus kloosii, Staphylococcus lugdunensis, and Staphylococcus saprophyticus, more preferably at least one selected from the group consisting of S. capitis and S. caprae strains, and particularly preferably at least one of S. capitis ATCC27840 and S. caprae ATCC35538. Furthermore, from the viewpoint of adjusting the balance of normal skin flora at the affected area to which the composition for treating tinea is applied, the other strains of the genus Staphylococcus preferably include strains of S. epidermidis (Staphylococcus epidermidis), and more preferably include at least one of S. epidermidis ATCC12228 and S. epidermidis ATCCC14990. These other strains of the genus Staphylococcus may be used alone or in combination of two or more.

[0077] The concentration of other Staphylococcus strains in the composition for treating tinea is not particularly limited, but may be 10 ３ ~10 １１ CFU / g, preferably 10 ４ ~10 １０ More preferably, 10 CFU / g ５ ~10 ９In addition, when two or more other strains of the genus Staphylococcus are contained in combination, it is preferable that each of the two or more other strains of the genus Staphylococcus falls within the above-mentioned range for each species.

[0078] The form of the other Staphylococcus strain in the composition for treating tinea is not particularly limited, but is preferably in the form of a dry powder (e.g., freeze-dried or spray-dried).The form of the other Staphylococcus strain is preferably the same as that of at least one selected from the group consisting of the above-mentioned S. hominis strain, S. haemolyticus strain, and S. warneri strain.

[0079] [Strains of other genera] The composition for treating tinea may further contain strains of other genera. Here, "strains of other genera" refers to bacterial strains other than strains of the genus Staphylococcus.

[0080] The strains of other genera are not particularly limited, but are preferably normal skin bacteria (i.e., normal skin bacteria other than Staphylococcus bacteria), and examples thereof include strains of Cutibacterium acnes, Streptococcus pyogenes (group A β-hemolytic streptococcus), Pseudomonas aeruginosa, Escherichia coli, Bacillus cereus, Enterococcus faecalis, and Moraxella osloensis.

[0081] Examples of Cutibacterium acnes strains include those listed in "NCBI," [online], archived February 17, 2022, [searched February 17, 2022], and the internet: <https: / / www.ncbi.nlm.nih.gov / genome / browse / #! / prokaryotes / 1140 / >. Examples of Streptococcus pyogenes (group A beta-hemolytic streptococcus) strains include those listed in "NCBI," [online], archived February 17, 2022, [searched February 17, 2022], and the internet: <https: / / www.ncbi.nlm.nih.gov / genome / browse / #! / prokaryotes / 175 / >. Examples of Pseudomonas aeruginosa strains include those listed in "NCBI", [online], archived February 17, 2022, [searched February 17, 2022], and the Internet <https: / / www.ncbi.nlm.nih.gov / genome / browse / #! / prokaryotes / 187 / >. Examples of Escherichia coli strains include those listed in "NCBI", [online], archived February 17, 2022, [searched February 17, 2022], and the Internet <https: / / www.ncbi.nlm.nih.gov / genome / browse / #! / prokaryotes / 167 / >. Examples of Bacillus cereus strains include those listed in "NCBI," [online], archived February 17, 2022, [searched February 17, 2022], and the internet: <https: / / www.ncbi.nlm.nih.gov / genome / browse / #! / prokaryotes / 157 / >. Examples of Enterococcus faecalis strains include those listed in "NCBI," [online], archived February 17, 2022, [searched February 17, 2022], and the internet: <https: / / www.ncbi.nlm.nih.gov / genome / browse / #! / prokaryotes / 808 / >.Examples of Moraxella osloensis strains include those listed in "NCBI," [online], archived February 17, 2022, [searched February 17, 2022], and on the Internet at <https: / / www.ncbi.nlm.nih.gov / genome / browse / #! / prokaryotes / 12468 / >.

[0082] Of these, from the viewpoint of obtaining a higher therapeutic effect against tinea, the strains of other genera preferably include at least one selected from the group consisting of Pseudomonas aeruginosa strains, Escherichia coli strains, Bacillus cereus strains, Enterococcus faecalis strains, and Moraxella osloensis strains, more preferably at least one selected from the group consisting of Pseudomonas aeruginosa strains, Escherichia coli strains, and Enterococcus faecalis strains, and even more preferably at least one selected from the group consisting of Pseudomonas aeruginosa ATCC27853, Escherichia coli ATCC25922, and Enterococcus faecalis ATCC29212. Furthermore, from the viewpoint of adjusting the balance of normal skin bacteria in the area to which the composition for treating tinea is applied, the strains of other genera preferably include at least one selected from the group consisting of strains of Cutibacterium acnes, strains of Streptococcus pyogenes (group A beta-hemolytic streptococcus), and strains of Pseudomonas aeruginosa, more preferably strains of Cutibacterium acnes, and even more preferably strains of Cutibacterium acnes ATCC 6919. These strains of other genera may be used alone or in combination of two or more.

[0083] The concentration of the strain of other genera in the composition for treating tinea is not particularly limited, but ３ ~10１１ CFU / g, preferably 10 ４ ~10 １０ More preferably, 10 CFU / g ５ ~10 ９ It is more preferable that the CFU / g is within the above range. When two or more strains of other genera are contained in combination, it is preferable that each of the two or more strains of other genera falls within the above range for each species.

[0084] The form of the strain of another genera in the composition for treating tinea is not particularly limited, but is preferably in the form of a dry powder (e.g., freeze-dried or spray-dried).The form of the strain of another genera is preferably the same as that of at least one selected from the group consisting of the above-mentioned S. hominis strain, S. haemolyticus strain, and S. warneri strain.

[0085] [Antifungal Agent] The composition for treating tinea may further contain an antifungal agent. By including an antifungal agent, the therapeutic effect against tinea may be further enhanced.

[0086] Antifungal agents include, but are not limited to, itraconazole, miconazole, clotrimazole, ketoconazole, bifonazole, lanoconazole, luliconazole, efinaconazole, fosravuconazole, terbinafine, butenafine, etc. These antifungal agents may be used alone or in combination of two or more.

[0087] The concentration of the antifungal agent in the composition for treating tinea is not particularly limited, but is preferably 0.1 to 30% by mass, and more preferably 0.5 to 15% by mass, relative to the total mass of the composition for treating tinea.

[0088] [Additives] The composition for treating tinea may contain additives. The additives are not particularly limited, but include bases, humectants, thickeners, emulsifiers, emulsifier aids, preservatives, stabilizers, pH adjusters, etc.

[0089] (Base) Examples of the base include a hydrophobic base, a hydrophilic base, and water. In this specification, the term "base" refers to an additive having a content of 40% by mass or more, preferably 50 to 99% by mass, relative to the total mass of the composition for treating tinea.

[0090] The hydrophobic base is not particularly limited, and examples thereof include higher hydrocarbons such as squalane, liquid paraffin, light liquid paraffin, petrolatum, ceresin wax, microcrystalline wax, squalene, and gelled hydrocarbons; oils and fats such as olive oil, jojoba oil, sesame oil, soybean oil, cacao butter, camellia oil, peanut oil, beef tallow, lard, triacetin, and hydrogenated castor oil; waxes such as beeswax, white beeswax, carnauba wax, and lanolin; fatty acids such as stearic acid and oleic acid; higher alcohols such as lanolin alcohol, myristyl alcohol, cetanol (cetyl alcohol), stearyl alcohol, cetostearyl alcohol, and cholesterol; and fatty acid esters such as isopropyl myristate, stearyl myristate, and medium-chain fatty acid triglycerides.

[0091] The hydrophilic base is not particularly limited, but examples thereof include lower alcohols such as ethanol, propanol, and isopropanol; polyhydric alcohols such as glycerin, 1,3-butylene glycol, and propylene glycol; sugar alcohols such as sorbitol and mannitol; and macrogol.

[0092] The above-mentioned bases may be used alone or in combination of two or more.

[0093] (Humectant) The humectant keeps the skin moist when the composition for treating ringworm is applied. Examples of the humectant include, but are not limited to, petrolatum, glycerin, propylene glycol, 1,3-butylene glycol, etc. The above-mentioned humectants may be used alone or in combination of two or more.

[0094] (Thickener) The thickener increases the viscosity or gels the composition for treating tinea. The thickener is not particularly limited, but includes gelatin, agar, carrageenan, gum arabic, tragacanth, sodium alginate, propylene glycol alginate, carboxyvinyl polymer, polyvinyl alcohol (partially saponified), sodium alginate, methylcellulose, carboxymethylcellulose, water-soluble cellulose derivatives (hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethylcellulose, hydrophobized hydroxypropylmethylcellulose, etc.), sodium polyacrylate, glycerin monooleate, pectin, xanthan gum, etc. The above-mentioned thickeners may be used alone or in combination of two or more.

[0095] (Emulsifier) ​​The emulsifier emulsifies the composition for treating tinea into an oil-in-water (o / w) type or a water-in-oil (w / o) type. Examples of the emulsifier include, but are not limited to, cationic surfactants such as alkylamine salts, alkylamine polyoxyethylene adducts, fatty acid triethanolamine monoester salts, acylaminoethyl diethylamine salts, and fatty acid polyamine condensates; anionic surfactants such as polyoxyethylene alkyl ether phosphates, alkyl sulfates, saturated higher fatty acid salts, and N-acylamino acid salts; nonionic surfactants such as sucrose fatty acid esters, glycerin fatty acid esters, polyglycerin fatty acid esters, polyoxyethylene fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, polyethylene glycol, polyethylene glycol fatty acid esters, polyoxyethylene polyoxypropylene glycol, and polyoxyethylene alkyl ethers; and zwitterionic surfactants such as alkyl betaines, alkylamido betaines, alkyl sulfobetaines, imidazolines, lauryl dimethylaminoacetic acid betaine, and alkyldiaminoethyl glycines. The above-mentioned emulsifiers may be used alone or in combination of two or more kinds.

[0096] (Emulsifier) ​​The emulsifier stabilizes the emulsion when the composition for treating tinea is emulsified into an oil-in-water (o / w) type or a water-in-oil (w / o) type. Examples of the emulsifier include, but are not limited to, cetanol (cetyl alcohol), stearyl alcohol, oleyl alcohol, isostearyl alcohol, etc. The above-mentioned emulsifiers may be used alone or in combination of two or more.

[0097] (Preservatives) The preservatives prevent or inhibit contamination and decomposition of the composition for treating tinea due to foreign microorganisms. Examples of preservatives include, but are not limited to, parahydroxybenzoic acid, methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, butyl parahydroxybenzoate, sodium benzoate, chlorobutanol, chlorocresol, benzyl alcohol, salicylic acid, phenoxyethanol, thymol, dibutylhydroxytoluene, sodium edetate hydrate, sodium dehydroacetate, sorbic acid, potassium sorbate, and benzalkonium chloride. The above-mentioned preservatives may be used alone or in combination of two or more.

[0098] (Stabilizer) The stabilizer prevents or inhibits the death, decomposition, and physical changes of the components contained in the composition for treating tinea. Examples of stabilizers include, but are not limited to, sodium bisulfite, sodium pyrosulfite, ascorbic acid, tocopherol, dibutylhydroxytoluene, sodium edetate (EDTA), benzotriazole, etc. The above-mentioned stabilizers may be used alone or in combination of two or more.

[0099] (pH adjuster) The pH adjuster maintains the stability of the components contained in the composition for treating tinea and prevents or reduces irritation of the composition for treating tinea to the living body. Examples of pH adjusters include, but are not limited to, lactic acid, acetic acid, acetate salts (sodium acetate, etc.), citric acid, citrate salts (sodium citrate, etc.), phosphoric acid, phosphate salts (sodium phosphate, etc.), diisopropanolamine, triisopropanolamine, triethanolamine, potassium hydroxide, sodium hydroxide, etc. The above-mentioned pH adjusters may be used alone or in combination of two or more.

[0100] [Dosage Form] The dosage form of the composition for treating tinea is not particularly limited, but is preferably an external preparation. By using the composition for treating tinea as an external preparation, at least one selected from the group consisting of S. hominis strains, S. haemolyticus strains, and S. warneri strains can be established on the skin, thereby effectively preventing or suppressing the growth and establishment of tinea fungi, and sterilizing or bacteriostasizing the fungi.

[0101] The specific form of the topical preparation is not particularly limited, but examples include ointments, creams, gels, lotions, and the like.

[0102] Ointments are semi-solid topical preparations in which the active ingredient to be applied to the skin is dissolved or dispersed in a base, and examples thereof include oily ointments and water-soluble ointments. Creams are semi-solid topical preparations emulsified as oil-in-water (o / w) or water-in-oil (w / o) to be applied to the skin. Gels are gel-like topical preparations to be applied to the skin, and examples thereof include aqueous gels and oily gels. Lotions are liquid topical preparations in which the active ingredient (e.g., S. hominis strain, S. haemolyticus strain, S. warneri strain) is dissolved or dispersed in an aqueous solution.

[0103] [Tinea fungus] The causative fungus of tinea is tinea fungus, specifically a fungus of the genus Trichophyton. Examples of the tinea fungus include fungal strains of Trichophyton rubrum, Trichophyton mentagrophytes, and Trichophyton tonsurans.

[0104] Examples of the fungal strain of Trichophyton rubrum include Trichophyton rubrum ATCC28188 and Trichophyton rubrum ATCC22402.

[0105] Examples of the fungal strain of Trichophyton mentagrophytes include Trichophyton mentagrophytes TIMM2789 and Trichophyton mentagrophytes ATCCMYA-4439.

[0106] Examples of the fungal strain of Trichophyton tonsurans include Trichophyton tonsurans ATCC56186 and Trichophyton tonsurans ATCC28942.

[0107] The causative fungus of tinea preferably includes a fungus of the genus Trichophyton, more preferably includes at least one selected from the group consisting of a fungal strain of Trichophyton rubrum, a fungal strain of Trichophyton mentagrophytes, and a fungal strain of Trichophyton tonsurans, further preferably includes a fungal strain of Trichophyton rubrum, and particularly preferably includes Trichophyton rubrum ATCC 28188. The causative fungus of tinea may be one type or two or more types.

[0108] Tinea is caused by the Trichophyton fungus. Tinea is classified into tinea pedis (athlete's foot), tinea unguium (tinea unguium), tinea manubriata (athlete's foot), tinea corporis (ringworm), tinea cruris (jock itch), tinea capitis (tinea capitis), etc. depending on the site of onset. Since the skin penetration of topical preparations varies depending on the site of onset, it is preferable to appropriately adjust the composition of the topical preparation depending on the site of onset.

[0109] [Administration Method] The administration method of the composition for treating tinea is not particularly limited, but when the composition for treating tinea is an external preparation, it is applied to the affected area.

[0110] The number of administrations (number of applications) is not particularly limited and may be three times a day, twice a day, once a day, once every two days, once every three days, once every four days, once every five days, once every six days, once every seven days, etc. Of these, the number of administrations is preferably once a day, once every two days, once every three days, once every four days, once every five days, once every six days, or once every seven days. The composition for treating tinea according to the present invention contains at least one strain selected from the group consisting of S. hominis strains, S. haemolyticus strains, and S. warneri strains, which have excellent skin adhesion properties. Therefore, compared to conventional tinea therapeutic agents, the composition can maintain remission and prevent recurrence due to the sustained effect associated with the adhesion of live bacteria, and can also reduce the number of administrations and improve patient compliance.

[0111] When the composition for treating tinea is used as an external preparation, the amount of application is 0.1 to 180 mg / cm ２ is preferably 1 to 10 mg / cm ２ In this case, it is more preferable that the amount of application of at least one selected from the group consisting of S. hominis strain, S. haemolyticus strain, and S. warneri strain in the composition for treating tinea is 10 0 ~10 8 CFU / cm ２ Preferably, 10 1 ~10 7 CFU / cm ２ More preferably, 2 ~10 6 CFU / cm ２ When the composition for treating tinea contains two or more strains of S. hominis, S. haemolyticus, and S. warneri, it is preferable that the total amount thereof is within the above range.

[0112] The affected area to which the composition for treating tinea is applied is not particularly limited, but is usually an area exhibiting symptoms of tinea. The composition for treating tinea according to the present invention contains at least one selected from the group consisting of strains of S. hominis, S. haemolyticus, and S. warneri, which are normal skin bacteria. Therefore, due to its high skin adhesion, the frequency of administration can be reduced compared to conventional topical preparations, and the problem of skin rash around the affected area does not occur or occurs very little, thereby increasing patient compliance.

[0113] The above-mentioned composition for treating tinea exhibits a therapeutic effect when used alone, but may also be used in combination with other therapeutic agents.

[0114] The other therapeutic agents include oral and topical agents. In this case, the oral or topical agent contains at least one antifungal agent such as itraconazole, miconazole, clotrimazole, ketoconazole, bifonazole, lanoconazole, luliconazole, efinaconazole, fosravuconazole, terbinafine, and butenafine. Two or more of the above-mentioned other therapeutic agents may be combined.

[0115] That is, according to one aspect of the present invention, a combination of a tinea therapeutic composition and another therapeutic agent is provided. In this case, when the tinea therapeutic composition is an external preparation, the other therapeutic agent is preferably an oral preparation. Furthermore, the tinea therapeutic composition and the other therapeutic agent may be administered simultaneously or sequentially.

[0116] <Method for Producing a Composition for Treating Tinea> One aspect of the present invention provides a method for producing a composition for treating tinea. The method includes the steps of (1) collecting and culturing a bacterial flora from at least one of the ankle and sole of a human (preferably a healthy individual without tinea symptoms), (2) isolating and culturing the cultured bacterial flora to obtain a candidate fungus, (3) evaluating the anti-tinea fungal activity of the candidate fungus to identify a bacterium with anti-tinea fungal activity, and (4) preparing a composition for treating tinea containing the bacterium with anti-tinea fungal activity. In this case, the bacterium with anti-tinea fungal activity includes at least one selected from the group consisting of S. hominis strains, S. haemolyticus strains, and S. warneri strains. Preferably, the S. hominis strain is an S. hominis strain with anti-tinea fungal activity. The S. haemolyticus strain is preferably an S. haemolyticus strain having an anti-trichophyton activity. The S. warneri strain is preferably an S. warneri strain having an anti-trichophyton activity. Specific examples of S. hominis strains, S. haemolyticus strains, and S. warneri strains are as described above.

[0117] [Step (1)] Step (1) is a step of collecting and culturing bacterial flora from at least one of the ankle and sole of a human (preferably a healthy individual without tinea symptoms). Bacterial flora is collected from the human ankle and / or sole using a swab or the like, and smeared on a medium for culture. This allows colonies to form for each bacterial strain.

[0118] [Step (2)] Step (2) is a step of isolating and culturing the bacterial flora cultured in step (1) to obtain candidate bacteria. The colonies formed by the culture in step (1) are each collected using a platinum loop or the like, and smeared on a medium for isolation and culture. This allows for the isolation of a large number of bacteria contained in the bacterial flora contained in the human ankle and / or sole. Note that each cultured bacterium is a candidate bacterium, and is preferably suspended in a bacterial stock solution and stored at a low temperature (e.g., −100 to −50°C, preferably −90 to −70°C) as a skin bacterial library.

[0119] [Step (3)] Step (3) is a step of evaluating the anti-trichophyton activity of the candidate fungus obtained in step (2) to identify a bacterium having anti-trichophyton activity.

[0120] In step (3), first, the candidate fungi isolated from the human ankles and / or soles are evaluated to determine which of them have anti-trichophyton activity. The anti-trichophyton activity of the candidate fungi is evaluated by the method described in "4. Evaluation of anti-trichophyton activity" in the Examples.

[0121] Next, bacteria with anti-trichophyton activity are selected and identified. Identification methods include, but are not limited to, methods based on 16S rDNA sequence comparison and methods for creating a phylogenetic tree. For example, in the method based on 16S rDNA sequence comparison, the 16S rDNA sequence of the target bacterium is analyzed, and the bacterium can be identified by performing a BLAST search of NCBI using the DNA sequence data. In the method for creating a phylogenetic tree, the 16S rDNA sequence of the bacterium is analyzed in combination with 16S rDNA sequence data of known bacteria to create a phylogenetic tree, and the target bacterium can be identified from the phylogenetic tree. Note that, if the target bacterium is identified as a S. hominis strain, S. haemolyticus strain, or S. warneri strain, step (3) may include a step of calculating the identity of the 16S rDNA sequence of the target bacterium to SEQ ID NOs: 1, 10, 17, etc., and a step of confirming the DNA sequence identity of the target bacterium.

[0122] The bacteria having anti-trichophyton activity identified in step (3) may include at least one selected from the group consisting of an S. hominis strain having anti-trichophyton activity, an S. haemolyticus strain having anti-trichophyton activity, and an S. warneri strain having anti-trichophyton activity. Therefore, by extracting at least one selected from the group consisting of a target S. hominis strain having anti-trichophyton activity, an S. haemolyticus strain having anti-trichophyton activity, and an S. warneri strain having anti-trichophyton activity from the stored skin bacteria library, it is possible to obtain an S. hominis strain having anti-trichophyton activity, an S. haemolyticus strain having anti-trichophyton activity, or an S. warneri strain having anti-trichophyton activity.

[0123] [Step (4)] Step (4) is a step of preparing a composition for treating tinea containing bacteria having anti-tinea fungal activity. The bacteria having anti-tinea fungal activity identified in step (3) are appropriately cultured, purified, lyophilized, or the like to prepare a composition for treating tinea containing bacteria having anti-tinea fungal activity. The bacteria having anti-tinea fungal activity include at least one selected from the group consisting of S. hominis strains, S. haemolyticus strains, and S. warneri strains, and preferably at least one selected from the group consisting of S. hominis strains having anti-tinea fungal activity, S. haemolyticus strains having anti-tinea fungal activity, and S. warneri strains.

[0124] <Treatment Method> According to one aspect of the present invention, there is provided a method for treating tinea. In this case, the treatment method comprises applying the above-mentioned composition for treating tinea to the affected area. The composition for treating tinea and its administration method are as described above.

[0125] The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples.

[0126] 1. Collection of candidate bacteria Bacterial flora was collected using swabs from one ankle and one sole of the foot of five healthy volunteers. The swabs containing the bacterial flora were streaked onto AnaeroColumbia RS blood agar medium and cultured at 35°C under aerobic conditions for one day. After culture, colonies characteristic of morphology, color, and dryness were collected using a platinum loop.

[0127] The platinum loop containing the collected colonies was smeared on an AnaeroColumbia RS blood agar medium and cultured for isolation at 35°C under aerobic conditions for one day.

[0128] After cultivation, the grown colonies were collected with a platinum loop, suspended in a 25% glycerol bacterial stock solution, and stored at -80°C. A total of 91 candidate strains were collected. 52 candidate strains were obtained from the ankle, and 39 candidate strains were obtained from the sole.

[0129] 2. Preparation of known bacteria The following 32 strains of bacteria were prepared as known bacteria. (1) Acinetobacter baumannii ATCC17978 (2) Corynebacterium glaucum JCM12208 (3) Corynebacterium jeikeium ATCC43734 (4) Corynebacterium striatum NBRC15291 (5) Enterococcus faecalis ATCC29212 (6) Escherichia coli ATCC25922 (7) Micrococcus luteus ATCC4698 (8) Moraxella atlantae NBRC14588 (9) Neisseria gonorrhoeae ATCC19424 (10) Pseudomonas aeruginosa ATCC27853 (11) Staphylococcus aureus ATCC29213 (12) Staphylococcus epidermidis ATCC12228 (13) Staphylococcus haemolyticus ATCC29970 (14) Staphylococcus hominis ATCC27844 (15) Streptococcus agalactiae ATCC13813 (16) Streptococcus mitis JCM12971 (17) Streptococcus pyogenes ATCC12344 (18) Staphylococcus aureus ATCC12600 (19) Staphylococcus epidermidis ATCC14990 (20) Staphylococcus capitis ATCC27840 (21) Staphylococcus caprae ATCC35538 (22) Staphylococcus cohnii ATCC29974 (23) Staphylococcus haemolyticus ATCC700564 (24) Staphylococcus haemolyticus ATCC29969 (25) Staphylococcus hominis ATCC27845 (26) Staphylococcushominis ATCC700236 (27) Staphylococcus kloosii ATCC43959 (28) Staphylococcus lentus ATCC700403 (29) Staphylococcus lugdunensis ATCC49576 (30) Staphylococcus lugdunensis ATCC43809 (31) Staphylococcus warneri ATCC27836 (32) Staphylococcus saprophyticus ATCC15305

[0130] 3. Preparation of Evaluation Medium In order to evaluate the anti-trichophyton activity of candidate fungi and known fungi, a fungal pour medium containing trichophyton was prepared as an evaluation medium.

[0131] Specifically, one bead of Trichophyton rubrum ATCC28188 stored in a microbank was taken, smeared on a potato dextrose agar (PDA) slant agar medium, and statically cultured at 30°C under aerobic conditions.

[0132] After the cultivation, phosphate buffered saline (PBS) containing 0.05% polysorbate 80 was added to the PDA agar slant medium to prepare a fungal inoculum.

[0133] PDA was dissolved in ultrapure water to a concentration of 39.0 g / L, and the resulting solution was heated in an autoclave (121°C, 20 minutes). After cooling, the PDA solution was mixed with the fungal inoculum solution, and the mixture was poured into petri dishes and solidified to prepare fungal pour medium.

[0134] 4. Evaluation of Anti-Trichophyton Activity The anti-trichophyton activity of candidate fungi (91 strains) and known fungi (32 strains) was evaluated using a fungal pour medium as an evaluation medium.

[0135] Specifically, one bead containing a candidate bacterium or a known bacterium stored in a microbank was taken, smeared on an AnaeroColumbia RS blood agar medium, and cultured at 35°C under aerobic conditions for 1 to 2 days, and the resulting bacteria were collected with a platinum loop.

[0136] The collected bacteria-containing platinum loop was streaked onto a fungal pour medium and incubated at 30°C under aerobic conditions until turbidity in the agar medium due to Trichophyton growth was visually confirmed. After incubation, the growth inhibition zone formed on the fungal pour medium was observed, and the anti-trichophyton activity of the candidate fungus or known fungus was evaluated according to the size of the growth inhibition zone according to the following criteria. Typical examples of each evaluation are shown in Figure 1.

[0137] ++: A clear area of ​​inhibition of tinea fungus growth was observed. +: No clear area of ​​inhibition of growth was observed, but inhibition of tinea fungus growth was observed. -: No inhibition of tinea fungus growth was observed.

[0138] First, the results obtained for known bacteria (32 strains) are shown in Table 4 below.

[0139]

[0140] The results in Table 4 show that, of the known bacteria (32 strains), 9 strains were "++", 10 strains were "+", and 13 strains were "-".

[0141] Furthermore, of the candidate bacteria (91 strains), 23 strains were "++", 32 strains were "+", and 36 strains were "-".

[0142] 5. Identification of candidate fungi To analyze the relationship between the anti-dermatophyte activity of the candidate fungi and the type of candidate fungi, we identified the candidate fungi by comparing their 16s rDNA sequences.

[0143] Specifically, total DNA was extracted and purified from candidate bacteria cultured on AnaeroColumbia RS blood agar medium according to the NucleoSpin Microbial DNA manual, and the DNA concentration and purity were measured using a NanoDrop ultra-microspectrophotometer.

[0144] Next, the 16S rDNA sequence region was amplified by PCR using the purified total DNA as a template and the included primers F1 (SEQ ID NO: 19) and R2 (SEQ ID NO: 20) according to the instructions in the Bacterial 16S rDNA PCR Kit. The amplified DNA fragment (approximately 1,500 bp) was purified using a NucleoSpin Gel and PCR Clean-up kit, and the DNA concentration and purity were measured using a NanoDrop ultra-microspectrophotometer. Agarose gel electrophoresis confirmed that the DNA fragment size was amplified as expected.

[0145] The amplified DNA fragment (16S rDNA template sample) was mixed with primers (F1 (SEQ ID NO: 19), F2 (SEQ ID NO: 21), or R2 (SEQ ID NO: 20)) provided with the Bacterial 16S rDNA PCR Kit, and the target sequence was analyzed by Sanger sequencing. After assembling the resulting sequences, the candidate bacterial species was identified by performing an NCBI BLAST search on the region between consensus sequence 1 (AGCTTGC) and consensus sequence 2 (AAGCTGG), which are shared by Staphylococcus 16S rDNA (approximately 1,240-1,280 bp). The target region of 16S rDNA (approximately 1,240-1,280 bp) is part of the amplified DNA fragment (approximately 1,500 bp) and contains consensus sequence 1 (AGCTTGC) and consensus sequence 2 (AAGCTGG). Furthermore, if consensus sequence 1 (AGCTTGC) was not present in the obtained sequence, it was replaced with GGTTGG and TGCTTGC in that order, and if consensus sequence 2 (AAGCTGG) was not present, it was replaced with GAAGTTGG, AAGTCGG, GAAGTCGA, AAGTCAG, GAGCTGG, AAGGGGGG, AAGTCTGG, CAGTCAG, and CCGCTGG in that order. The candidate bacterial species were identified by performing a BLAST search using NCBI on the base sequence of the region flanked by each consensus sequence (approximately 1,240 to 1,280 bp). If the obtained sequence did not contain either or both of consensus sequence 1 (AGCTTGC) or its alternative sequences (GGTTGG, TGCTTGC), and consensus sequence 2 (AAGCTGG) or its alternative sequences (GAAGTTGG, AAGTCGG, GAAGTCGA, AAGTCAG, GAGCTGG, AAGGGGGG, AAGTCTGG, CAGTCAG, CCGCTGG), the candidate bacterial species was identified by performing an NCBI BLAST search on the full-length base sequence of the obtained sequence (amplified DNA fragment (approximately 1,500 bp)).

[0146] To identify the candidate bacterial species, we selected species that showed 99% or more identity from the top 10 sequences found in the BLAST search. If the top 10 selected species included multiple results from the same genus but different species, we used the genus name (Staphylococcus sp. and Micrococcus sp.). If no species meeting the criteria was identified, the species was classified as unknown.

[0147] The identified candidate fungi and the results of their anti-trichophyton activity are shown in Tables 5 and 6 below.

[0148]

[0149]

[0150] The identified candidate bacteria are organized by species in Tables 5 and 6, and the percentage of anti-tinea fungal activity exhibited by each species is analyzed and shown in Figure 2. The results in Figure 2 indicate that 100% and 86% of Staphylococcus hominis and Staphylococcus haemolyticus, respectively, showed a "++" result.

[0151] Of the 92 candidate strains, 52 strains were isolated from the ankles and 39 strains were isolated from the soles of the feet. The results of their anti-trichophyton activity by isolation site are shown in Table 7 below.

[0152]

[0153] From the results in Table 7, of the 52 strains from the ankle, 33% were "++", 31% were "+", and 37% were "-", and of the 39 strains from the soles, 15% were "++", 41% were "+", and 44% were "-". It was found that the proportion of strains showing "++" was approximately twice as high in the ankle as in the soles.

[0154] 6. Creation of a phylogenetic tree of the genus Staphylococcus A phylogenetic tree was created for 27 known strains of Staphylococcus (Table 8 below) and 45 candidate strains identified as Staphylococcus (Tables 5 and 6 are shown in Table 9 below) based on a phylogenetic tree based on the 16S rDNA sequences of 27 Staphylococcus species in a paper by Ghebremedhin B et al. (J Clin Microbiol, 2008;46:1019-1025: Genetic classification and distinguishing of Staphylococcus species based on different partial gap, 16S rRNA, hsp60, rpoB, sodA, and tuf gene sequences). The phylogenetic tree is shown in Figure 3. The phylogenetic tree was created using CLC sequence viewer (ver. 8.0).

[0155]

[0156]

[0157] Comparing the phylogenetic tree in Figure 3 with the results of the anti-dermatophyte activity of the candidate fungi, the clusters were roughly divided into three clusters: cluster 1, which mainly showed "-" results, cluster 2, which mainly showed "++" results, and cluster 3, which mainly showed "+" results. Of these, cluster 2 consisted of S. hominis and S. haemolyticus.

[0158] Therefore, a phylogenetic tree was created for six known strains of S. hominis and S. haemolyticus bacteria (Table 10 below) and 15 candidate strains identified as S. hominis or S. haemolyticus (Table 11 below, excerpts from Table 9). The created phylogenetic trees for S. hominis and S. haemolyticus are shown in Figures 4 and 5.

[0159]

[0160]

[0161] 7. 16s rDNA Sequence (1) 16s rDNA Sequence of Staphylococcus hominis Strains The 16s rDNA sequence of the known bacterium Staphylococcus hominis ATCC27844 was confirmed in the ATCC database, and the nucleotide sequence of the region flanked by consensus sequence 1 (AGCTTGC) and consensus sequence 2 (AAGCTGG) was confirmed. As a result, the 16s rDNA sequence of Staphylococcus hominis ATCC27844 had the nucleotide sequence of SEQ ID NO: 1 (Staphylococcus hominis ATCC27844 genome position: 716544-717811). Note that SEQ ID NO: 1 contains consensus sequence 1 (AGCTTGC) and consensus sequence 2 (AAGCTGG), and therefore the 5' end of the nucleotide sequence of SEQ ID NO: 1 is consensus sequence 1 (AGCTTGC), and the 3' end is consensus sequence 2 (AAGCTGG).

[0162] Furthermore, the 16s rDNA sequences of candidate strains Nos. 2, 3, 37, 40, 45, 62, 64, and 74, which were identified as Staphylococcus hominis strains, were confirmed for the nucleotide sequences (approximately 1,240 to 1,280 bp) of the regions flanked by consensus sequence 1 (AGCTTGC) and consensus sequence 2 (AAGCTGG) using the same method as described above in "5. Identification of candidate strains." As a result, the 16s rDNA sequences of candidate strains Nos. 3, 40, 45, 64, and 74 had the nucleotide sequence of SEQ ID NO: 5, the 16s rDNA sequence of candidate strain No. 2 had the nucleotide sequence of SEQ ID NO: 7, the 16s rDNA sequence of candidate strain No. 37 had the nucleotide sequence of SEQ ID NO: 8, and the 16s rDNA sequence of candidate strain No. 62 had the nucleotide sequence of SEQ ID NO: 9.

[0163] Furthermore, the 16s rDNA sequences of the known bacteria Staphylococcus hominis ATCC27845 and Staphylococcus hominis ATCC700236 were confirmed in the ATCC database, and the base sequence of the region flanked by consensus sequence 1 (AGCTTGC) and consensus sequence 2 (AAGCTGG) was confirmed. Also, the 16s rDNA sequence of Staphylococcus hominis A9 (ATCC accession number: PTA-125203) was confirmed in the PATRIC database, and the base sequence of the region flanked by consensus sequence 1 (AGCTTGC) and consensus sequence 2 (AAGCTGG) was confirmed. As a result, the 16s rDNA sequence of Staphylococcus hominis ATCC27845 had the nucleotide sequence of SEQ ID NO: 1 (Staphylococcus hominis ATCC27845 genome position: 761822-763089), and the 16s rDNA sequences of Staphylococcus hominis ATCC700236 and Staphylococcus hominis A9 (ATCC accession number: PTA-125203) had the nucleotide sequences of SEQ ID NO: 5 (Staphylococcus hominis ATCC700236 genome position: 849942-851209, Staphylococcus hominis A9 genome position: 185-1452).

[0164] (2) 16s rDNA sequence of Staphylococcus haemolyticus strains The 16s rDNA sequence of the known bacterium Staphylococcus haemolyticus ATCC29970 was confirmed in the ATCC database, and the nucleotide sequence of the region flanked by consensus sequence 1 (AGCTTGC) and consensus sequence 2 (AAGCTGG) was confirmed. As a result, the 16s rDNA sequence of Staphylococcus haemolyticus ATCC29970 had the nucleotide sequence of SEQ ID NO: 10 (Staphylococcus haemolyticus ATCC29970 genome position: 807302-808569).

[0165] Furthermore, the 16s rDNA sequences of candidate strains Nos. 22 to 25, 33, and 35, which were identified as Staphylococcus haemolyticus strains, were confirmed for the nucleotide sequences (approximately 1,240 to 1,280 bp) of the regions flanked by consensus sequence 1 (AGCTTGC) and consensus sequence 2 (AAGCTGG) using the same method as described above in "5. Identification of candidate strains." As a result, the 16s rDNA sequences of candidate strains Nos. 22, 24, 25, and 33 had the nucleotide sequence of SEQ ID NO: 13, the 16s rDNA sequence of candidate strain No. 35 had the nucleotide sequence of SEQ ID NO: 14, and the 16s rDNA sequence of candidate strain No. 23 had the nucleotide sequence of SEQ ID NO: 16. The 16s rDNA sequence of candidate strain No. 20, which was identified as a Staphylococcus haemolyticus strain, contained consensus sequence 1 (AGCTTGC) but not consensus sequence 2 (AAGCTGG). The 16s rDNA sequence of No. 20 contained an alternative sequence (GAGCTGG) to consensus sequence 2, so the base sequence (approximately 1,267 bp) of the region flanked by consensus sequence 1 (AGCTTGC) and the alternative sequence (GAGCTGG) to consensus sequence 2 was confirmed. As a result, the 16s rDNA sequence of candidate No. 20 contained the base sequence of SEQ ID NO: 15.

[0166] Furthermore, the 16s rDNA sequence of the known bacterium Staphylococcus haemolyticus ATCC700564 was checked against the ATCC database, and the nucleotide sequence of the region flanked by consensus sequence 1 (AGCTTGC) and consensus sequence 2 (AAGCTGG) was confirmed. As a result, the 16s rDNA sequence of Staphylococcus haemolyticus ATCC700564 had the nucleotide sequence of SEQ ID NO: 10 (Staphylococcus haemolyticus ATCC700564 genome position: 214068-215335).

[0167] The results obtained in (1) and (2) above are shown in Tables 12 and 13 below.

[0168]

[0169]

[0170] In Table 13, SEQ ID NOs: 5 and 7 to 9 are based on SEQ ID NO: 1, and SEQ ID NOs: 13 to 16 are based on SEQ ID NO: 10. For example, "45G>A" in SEQ ID NO: 5 means that G (guanine) at position 45 of SEQ ID NO: 1 has been mutated to A (adenine). For example, "488delA" in SEQ ID NO: 7 means that A (adenine) at position 488 of SEQ ID NO: 1 has been deleted. For example, "1182_1183insA" in SEQ ID NO: 8 means that A (adenine) has been inserted between positions 1182 and 1183 of SEQ ID NO: 1.

[0171] (3) 16s rDNA sequence of Staphylococcus warneri strains The 16s rDNA sequence of the known bacterium Staphylococcus warneri ATCC27836 was confirmed in the ATCC database, and the nucleotide sequence of the region flanked by consensus sequence 1 (AGCTTGC) and consensus sequence 2 (AAGCTGG) was confirmed. As a result, the 16s rDNA sequence of Staphylococcus warneri ATCC27836 had the nucleotide sequence of SEQ ID NO: 17 (Staphylococcus warneri ATCC27836 genome position: 725369-726636).

[0172] From the results of 7(1) to (3) above, it is believed that S. hominis having 16s rDNA containing SEQ ID NO: 1 or a nucleotide sequence having 95% or more identity with SEQ ID NO: 1, S. haemolyticus having 16s rDNA containing SEQ ID NO: 10 or a nucleotide sequence having 95% or more identity with SEQ ID NO: 10, and S. warneri having 16s rDNA containing SEQ ID NO: 17 or a nucleotide sequence having 95% or more identity with SEQ ID NO: 17 have anti-tinea fungal activity.

[0173] 8. Effect on other dermatophytes In the above sections 4 to 7, a fungal pour medium containing the dermatophyte Trichophyton rubrum ATCC28188 was used as the evaluation medium (see "3. Preparation of evaluation medium" above). Here, the effect on other dermatophytes (dermatophytes other than T. rubrum ATCC28188) was evaluated.

[0174] (1) Preparation of fungal pour medium containing other dermatophytes Fungal pour medium containing five species of dermatophytes was prepared in the same manner as in "3. Preparation of evaluation medium" above, except that Trichophyton rubrum ATCC28188 beads were replaced with Trichophyton rubrum ATCC22402 beads, Trichophyton mentagrophytes TIMM2789 beads, Trichophyton mentagrophytes ATCCMYA-4439 beads, Trichophyton tonsurans ATCC56186 beads, or Trichophyton tonsurans ATCC28942 beads.

[0175] (2) Evaluation of anti-tinea fungal activity against other tinea fungi The anti-tinea fungal activity of the known fungi S. hominis ATCC27844, S. hominis ATCC27845, S. haemolyticus ATCC29969, S. haemolyticus ATCC700564, and S. warneri ATCC27836, which were evaluated for their anti-tinea fungal activity against Trichophyton rubrum ATCC28188, was evaluated using fungal pour medium containing the above five species of tinea fungi.

[0176] The evaluation method was the same as in "4. Evaluation of anti-trichophyton activity" above. The results obtained are shown in Table 13 below, along with the results of the anti-trichophyton activity against T. rubrum ATCC28188.

[0177]

[0178] The results in Table 14 show that the same anti-dermatophytic activity as that of T. rubrum ATCC28188 was also exhibited against five other types of dermatophytes.

Claims

1. A composition for treating ringworm, comprising at least one selected from the group consisting of a strain of Staphylococcus hominis, a strain of Staphylococcus haemolyticus, and a strain of Staphylococcus warneri.

2. The composition for treating ringworm according to claim 1, comprising a strain of Staphylococcus hominis.

3. 3. The composition for treating tinea according to claim 2, wherein the Staphylococcus hominis strain has a 16s rDNA containing the base sequence of SEQ ID NO: 1 or a 16s rDNA containing a base sequence having 95% or more identity to SEQ ID NO: 1, and has anti-tinea activity.

4. 3. The composition for treating tinea according to claim 2, wherein the Staphylococcus hominis strain comprises at least one selected from the group consisting of Staphylococcus hominis ATCC27844, Staphylococcus hominis ATCC27845, Staphylococcus hominis ATCC700236, and Staphylococcus hominis A9 (ATCC Accession Number: PTA-125203).

5. The composition for treating tinea according to claim 1, comprising a strain of Staphylococcus haemolyticus.

6. 6. The composition for treating tinea according to claim 5, wherein the Staphylococcus haemolyticus strain has a 16s rDNA containing the base sequence of SEQ ID NO: 10 or a 16s rDNA containing a base sequence having 95% or more identity to SEQ ID NO: 10, and has anti-tinea activity.

7. 6. The composition for treating tinea according to claim 5, wherein the Staphylococcus haemolyticus strain comprises at least one selected from the group consisting of Staphylococcus haemolyticus ATCC29970, Staphylococcus haemolyticus ATCC700564, and Staphylococcus haemolyticus ATCC29969.

8. The composition for treating ringworm according to claim 1, comprising a strain of Staphylococcus warneri.

9. The composition for treating tinea described in claim 8, wherein the Staphylococcus warneri strain has a 16s rDNA containing the base sequence of SEQ ID NO: 17 or a 16s rDNA containing a base sequence having 95% or more identity to SEQ ID NO: 17, and has anti-tinea activity.

10. The composition for treating tinea according to claim 8, wherein the strain of Staphylococcus warneri comprises Staphylococcus warneri ATCC27836.

11. The composition for treating tinea according to any one of claims 1 to 10, wherein the causative fungus of tinea comprises a fungus of the genus Trichophyton.

12. The composition for treating tinea according to claim 11, wherein the causative fungus of tinea comprises at least one selected from the group consisting of fungal strains of Trichophyton rubrum, Trichophyton mentagrophytes, and Trichophyton tonsurans.

13. The composition for treating tinea according to any one of claims 1 to 10, which is an external preparation.

14. (1) collecting and culturing bacterial flora from at least one of a human ankle and a human foot sole; (2) isolating and culturing the cultured bacterial flora to obtain candidate bacteria; (3) evaluating the anti-trichophyton activity of the candidate fungus to identify a bacterium having anti-trichophyton activity; (4) a step of preparing a composition for treating tinea, which comprises the bacterium having anti-tinea fungal activity; Including, A method for producing a composition for treating tinea, wherein the bacterium having anti-tinea fungal activity comprises at least one selected from the group consisting of a strain of Staphylococcus hominis, a strain of Staphylococcus haemolyticus, and a strain of Staphylococcus warneri.

15. Use of at least one strain selected from the group consisting of a strain of Staphylococcus hominis, a strain of Staphylococcus haemolyticus, and a strain of Staphylococcus warneri in the manufacture of a drug for treating ringworm.

16. The use of claim 15, comprising a strain of Staphylococcus hominis.

17. The use described in claim 16, wherein the Staphylococcus hominis strain has 16s rDNA containing the base sequence of SEQ ID NO: 1 or 16s rDNA containing a base sequence having 95% or more identity to SEQ ID NO: 1, and has anti-tinea activity.

18. The use described in claim 16, wherein the Staphylococcus hominis strain includes at least one selected from the group consisting of Staphylococcus hominis ATCC27844, Staphylococcus hominis ATCC27845, Staphylococcus hominis ATCC700236, and Staphylococcus hominis A9 (ATCC accession number: PTA-125203).

19. The use of claim 15, comprising a strain of Staphylococcus haemolyticus.

20. The use described in claim 19, wherein the Staphylococcus haemolyticus strain has 16s rDNA containing the base sequence of SEQ ID NO: 10, or 16s rDNA containing a base sequence having 95% or more identity to SEQ ID NO: 10, and has anti-tinea activity.

21. The use described in claim 19, wherein the Staphylococcus haemolyticus strain includes at least one selected from the group consisting of Staphylococcus haemolyticus ATCC29970, Staphylococcus haemolyticus ATCC700564, and Staphylococcus haemolyticus ATCC29969.

22. The use of claim 15, comprising a strain of Staphylococcus warneri.

23. The use described in claim 22, wherein the Staphylococcus warneri strain has a 16s rDNA containing the base sequence of SEQ ID NO: 17 or a 16s rDNA containing a base sequence having 95% or more identity to SEQ ID NO: 17, and has anti-tinea activity.

24. The use described in claim 22, wherein the strain of Staphylococcus warneri includes Staphylococcus warneri ATCC27836.

25. The use described in any one of claims 15 to 24, wherein the causative fungus of tinea includes a fungus of the genus Trichophyton.

26. The use described in claim 25, wherein the causative fungus of ringworm comprises at least one selected from the group consisting of fungal strains of Trichophyton rubrum, fungal strains of Trichophyton mentagrophytes, and fungal strains of Trichophyton tonsurans.

27. ​​The use described in any one of claims 15 to 24, which is an external preparation.

28. Use of at least one selected from the group consisting of strains of Staphylococcus hominis, strains of Staphylococcus haemolyticus, and strains of Staphylococcus warneri in the treatment of ringworm.

29. The use of claim 28, comprising a strain of Staphylococcus hominis.

30. The use described in claim 29, wherein the Staphylococcus hominis strain has 16s rDNA containing the base sequence of SEQ ID NO: 1 or 16s rDNA containing a base sequence having 95% or more identity to SEQ ID NO: 1, and has anti-tinea activity.

31. The use described in claim 29, wherein the Staphylococcus hominis strain includes at least one selected from the group consisting of Staphylococcus hominis ATCC27844, Staphylococcus hominis ATCC27845, Staphylococcus hominis ATCC700236, and Staphylococcus hominis A9 (ATCC accession number: PTA-125203).

32. The use of claim 28, comprising a strain of Staphylococcus haemolyticus.

33. The use described in claim 32, wherein the Staphylococcus haemolyticus strain has 16s rDNA containing the base sequence of SEQ ID NO: 10, or 16s rDNA containing a base sequence having 95% or more identity to SEQ ID NO: 10, and has anti-tinea activity.

34. The use described in claim 32, wherein the Staphylococcus haemolyticus strain includes at least one selected from the group consisting of Staphylococcus haemolyticus ATCC29970, Staphylococcus haemolyticus ATCC700564, and Staphylococcus haemolyticus ATCC29969.

35. The use of claim 28, comprising a strain of Staphylococcus warneri.

36. The use described in claim 35, wherein the Staphylococcus warneri strain has 16s rDNA containing the base sequence of SEQ ID NO: 17 or 16s rDNA containing a base sequence having 95% or more identity to SEQ ID NO: 17, and has anti-tinea activity.

37. The use described in claim 35, wherein the strain of Staphylococcus warneri includes Staphylococcus warneri ATCC27836.

38. The use described in any one of claims 28 to 37, wherein the causative fungus of tinea includes a fungus of the genus Trichophyton.

39. The use described in claim 38, wherein the causative fungus of ringworm comprises at least one selected from the group consisting of fungal strains of Trichophyton rubrum, fungal strains of Trichophyton mentagrophytes, and fungal strains of Trichophyton tonsurans.

40. The use described in any one of claims 28 to 37, which is an external preparation.