bacterial strain, composition, and method of use

Abstract

To provide a bacterial strain for treating a pathogenic bacterial infection in a subject such as a mammal, and a composition comprising the bacterial strain.SOLUTION: The present invention relates to a bacterial strain selected from Lactobacillus plantarum, where the Lactobacillus plantarum is Lactobacillus plantarum LB244R, which is deposited as DSM32996; or Lactobacillus plantarum LB356R, which is deposited as DSM33094.SELECTED DRAWING: None

Description

[Technical Field]

[0001] This invention relates to a novel bacterial staining method. In particular, this invention treats and slows the growth of pathogenic microorganisms. Novel for use in the context of suppressing, preventing, and / or preventing Regarding bacterial strains. [Background technology]

[0002] Staphylococcus aureus, a Gram-positive bacterium. It is one of the most frequently encountered human pathogens. Staphylococcus aureus is found in the nasal cavity of humans. It is particularly common in [location], and is either intermittent or persistent in about 50% of the human population. It can be observed in the skin. Staphylococcus aureus colonies are almost always asymptomatic, but skin When the protective barrier function is impaired, pathogens can cause infection. Therefore Staphylococcal infections can cause dermatitis, eczema, carbuncles, cellulitis, rosacea, psoriasis, diaper rash, and impetigo. It is often associated with skin conditions such as rashes and wounds.

[0003] An example of a skin infection is atopic dermatitis, which is caused by environmental factors, immunological factors, Chronic or chronically relapsing conditions resulting from a complex interplay of genetic and pharmacological factors. It is an inflammatory skin disease.

[0004] All of these genetic and environmental factors contribute to the following characteristics: 1: (Normal Staphylococcus epidermidis) Compared to (dis), abnormal microbial colony formation caused by pathogenic organisms such as Staphylococcus aureus. Subsequently, the patient's susceptibility to skin infections increased, and in addition, Staphylococcus aureus It produces enterotoxins and induces the production of enterotoxin-specific IgE, and this This results in greater T cell recruitment, 2: Involved in the initial phase of the disease, which in turn leads to immunoglobulin E (IgE) production. Raise it 3: Skin barrier function resulting from abnormal lipid metabolism and / or epidermal structural protein formation Incomplete or dry skin, as 4: Along with the psychosomatic effects on patients caused by autonomic nervous system imbalance, various subsequent symptoms The production of mediators from inflammatory cells increases.

[0005] Atopic dermatitis is typically treated with topical moisturizers / dermatological treatments as the first-line therapy. Patients who are not controlled with emollients or corticosteroids followed by first-line treatment For those patients, treatment is second-line with topical calcineurin inhibitors.

[0006] Currently, local thinning of the skin at the application site, worsening or risk of acne in patients, Patients with mild to moderate atopic dermatitis who do not experience serious side effects such as burning sensations. There is no localized treatment for this.

[0007] The unmet demand for atopic dermatitis patients remains. Local treatment still causes distress to the patient as itching, a well-known side effect. This simply worsens disease symptoms, leading to lichenification, epidermal exfoliation, and destruction of the skin barrier. This creates a vicious cycle for those suffering from the disease, increasing the risk of skin infections.

[0008] The most difficult and unmet needs that have yet to be addressed are those related to Staphylococcus aureus, in particular. Prevention and treatment of skin infections caused by Staphylococcus that is resistant to antibiotics, avoiding additional antibiotic resistance which is.

[0009] Even more different pathogenic microorganisms have been discovered, which may include bacterial microorganisms, viral microorganisms, fungal microorganisms, parasitic microorganisms, and algal microorganisms, and Staphylococcus aureus, a Gram-positive bacterium, is one of the most frequently encountered human pathogens.

[0010] Since penicillin was discovered in 1928 and mass-produced in the early 1940s, infections caused by Staphylococcus aureus could usually be treated without any major complications. However, clinicians immediately observed the emergence of penicillin-resistant strains of Staphylococcus aureus, which was mainly due to the expression of an enzyme called β-lactamase in bacteria that destroys the β-lactam ring structure of penicillins and cephalosporins (β-lactam antibiotics), thereby destroying their antibacterial activity. Methicillin, a new penicillin-like substance resistant to beta-lactamase, was introduced in 1959 and was initially effective against penicillin-resistant Staphylococcus aureus strains. However, the first methicillin-resistant Staphylococcus aureus (MR SA) strain was identified in the laboratory by 1961, and cases of MRSA were first observed in a clinic in 1968, so this success was short-lived.

[0011] MRSA infections mainly occur in the hospital environment, and MRSA is currently one of the most common nosocomial pathogens and is therefore a major cause of various healthcare-associated infections (HAIs). Since 19 90, a new type of MRSA known as community-associated MRSA (CA-MRSA) ​RSA has appeared. CA-MRSA is genetically distinct from healthcare-associated MRSA (HA-MRSA) strains. Not only can they be distinguished, but they can also exhibit different toxicity and antibiotic resistance patterns. In recent years, hybridization between different CA-MRSA and HA-MRSA strains has been observed. This often makes it difficult to determine the origin of the infecting MRSA strain.

[0012] HA-MRSA infection is associated with major clinical complications, including the need for mechanical ventilation. Patients, and those with surgical wounds or surgical implants, or those who have undergone surgical wound removal. It frequently occurs in patients who require fluids. Moreover, HA-MRSA infections are often hospital-related. This can lead to internal pneumonia or bacteremia, which are associated with high morbidity and mortality rates.

[0013] Staphylococcus aureus infects not only humans but also other mammals, so infection can occur. Livestock and pets are additional sources of infection. Livestock-associated MRSA (LA-MRSA) They are mostly identified in pig populations, and their colony formation rates vary dramatically from 10% to 80%. However, LA-MRSA has also been found in ruminants and poultry.

[0014] LA-MRSA is becoming an increasing problem for the livestock industry. Stables, barns, animals Property, agricultural workers, families of agricultural workers, owners and visitors of stables, as well as slaughterhouses and Animal transport vehicles and similar items are contaminated with LA-MRSA. These items are LA-MR SA can be present, LA-MRSA can be transferred between subjects, and therefore healthy carriers This could be the reason for the transmission of LA-MRSA among individuals, and also M RSA can enter hospitals or nursing homes via carriers, and can cause eczema and atopic dermatitis. Patients suffering from inflammatory skin diseases such as carbuncles, cellulitis, rosacea, psoriasis, wounds, and burns. , or resulting in diaper rash and impetigo caused by MRSA. This may also carry an additional risk of transmission to humans, including children and infants.

[0015] Therefore, treatment of pathogenic microorganisms such as MRSA would be advantageous, especially if currently available Effective treatment for eczema and atopic dermatitis, carbuncles, cellulitis, rosacea, psoriasis, wounds and burns. It does not result in any adverse effects such as inflammatory skin diseases, or diaper rash and impetigo. It is free from any adverse effects on humans, including children and infants, and furthermore This leads to resistance, for example, a more efficient method that does not induce antibiotic resistance in pathogenic microorganisms. A reliable and trustworthy approach would be advantageous. [Overview of the project] [Problems that the invention aims to solve]

[0016] Therefore, the object of the present invention is to treat pathogenic bacterial infections in subjects such as mammals. This relates to microorganisms, compositions, and methods for this purpose. [Means for solving the problem]

[0017] In particular, the object of the present invention is to treat pathogenic bacterial infections in mammals and other subjects. , skin infections, skin diseases, morbidity, and mortality due to infection and antibiotic resistance The aim is to provide microorganisms, compositions, and methods that solve the aforementioned problems of the prior art.

[0018] Therefore, one aspect of the present invention is: -As DSM32906 International Weissella viridescens LB10G, which is on deposit; -As DSM32907 International Lactobacillus paracasei LB113R is being deposited; -As DSM32996 International Lactobacillus plantarum LB244R is on deposit; -As DSM32908 International Lactobacillus paracasei LB116R deposited; -As DSM32997 International Enterococcus faecium LB276R is currently on deposit; -As DSM33091 International Lactobacillus plantarum LB316R is being deposited; -Leuconostoc mesenteriodes LB341R; -As DSM33093 International The deposited Leuconostok mesenteriodes LB349R; -As DSM33094 International Lactobacillus plantarum LB356R is being deposited; -As DSM33098 International Lactobacillus plantarum LB312R is being deposited; This relates to bacterial strains that have at least 95% genetic homology to one or more bacterial strains selected from the group consisting of [the specified group].

[0019] Therefore, another aspect of the present invention is, -Deposited as DSM32906: Weissera viridecens LB10G; -Lactobacillus paracasei LB113R deposited as DSM32907; -Lactobacillus plantarum LB244R deposited as DSM32996 ; -Lactobacillus paracasei LB116R deposited as DSM32908; -Enterococcus faecium LB276R deposited as DSM32997 ; -Lactobacillus plantarum LB316R deposited as DSM33091 ; - Deposited as DSM33093: Leuconostok mesenteriodes LB34 9R; -Lactobacillus plantarum LB356R deposited as DSM33094 ; -Lactobacillus plantarum LB312R deposited as DSM33098 ; At least 95% genetic information is obtained for one or more bacterial strains selected from the group consisting of the following: Regarding homologous bacterial strains.

[0020] Another aspect of the present invention relates to a composition comprising one or more bacterial strains according to the present invention.

[0021] Yet another aspect of the present invention relates to treating, mitigating, inhibiting, and preventing the growth of pathogenic microorganisms; and / The present invention relates to compositions for use in preventing or otherwise preventing the invention.

[0022] Detailed description of the invention This invention aims to prevent or treat infectious diseases caused by pathogenic microorganisms, such as staphylococcal infections. This invention relates to probiotic bacteria and compositions for use in MR. Compositions that can inhibit the growth of pathogenic microorganisms such as SA, and also new microbial strains. To relate to.

[0023] MRSA is transmitted through sharing personal items that have come into contact with infected skin, or through skin contact. By touching contaminated objects such as the nasal cavity, animals, surfaces, or objects, etc. , via carriers, for example, an infected surface or direct contact with another infected person, from one target to another It can expand in that way.

[0024] Despite improvements in treatment, invasive MRSA infections, particularly those occurring in community or livestock environments, persist. This remains a problem, and in addition to the substantial discomfort it causes to patients, the healthcare system This ultimately results in a significant financial burden for M. Similarly, in the European Union, MRSA is, 44% of all healthcare-associated infections (HAIs), 22% of attributable extra deaths, and HAI MRSA accounts for 41% of the extra hospital days related to it. MRSA is found in various strains of Staphylococcus aureus. Japan has one of the highest crude prevalence rates of MRSA in the world, making it a serious public health issue. The above concerns.

[0025] This invention inhibits the growth of Staphylococcus aureus without contributing to the further development of antibiotic resistance. This provides novel microbial strains and new compositions that can be used.

[0026] Therefore, preferred embodiments of the present invention are -Deposited as DSM32906: Weissera viridecens LB10G; -Lactobacillus paracasei LB113R deposited as DSM32907; -Lactobacillus plantarum LB244R deposited as DSM32996 ; -Lactobacillus paracasei LB116R deposited as DSM32908; -Enterococcus faecium LB276R deposited as DSM32997 ; -Lactobacillus plantarum LB316R deposited as DSM33091 ; -Leuconostok mesenteriodes LB341R; - Deposited as DSM33093: Leuconostok mesenteriodes LB34 9R; -Lactobacillus plantarum LB356R deposited as DSM33094 ; -Lactobacillus plantarum LB312R deposited as DSM33098 ; At least 95% genetic information is obtained for one or more bacterial strains selected from the group consisting of the following: Regarding homologous bacterial strains.

[0027] Therefore, another preferred embodiment of the present invention is: -Deposited as DSM32906: Weissera viridecens LB10G; -Lactobacillus paracasei LB113R deposited as DSM32907; -Lactobacillus plantarum LB244R deposited as DSM32996 ; -Lactobacillus paracasei LB116R deposited as DSM32908; -Enterococcus faecium LB276R deposited as DSM32997 ; -Lactobacillus plantarum LB316R deposited as DSM33091 ; - Deposited as DSM33093: Leuconostok mesenteriodes LB34 9R; -Lactobacillus plantarum LB356R deposited as DSM33094 ; -Lactobacillus plantarum LB312R deposited as DSM33098 ; At least 95% genetic information is obtained for one or more bacterial strains selected from the group consisting of the following: Regarding homologous bacterial strains.

[0028] In this context, the term "genetic homology" refers to the relationship between a bacterial strain and a deposited bacterial strain. Regarding deviations in gene sequences.

[0029] In embodiments of the present invention, genetic homology is -Deposited as DSM32906: Weissera viridecens LB10G; -Lactobacillus paracasei LB113R deposited as DSM32907; -Lactobacillus plantarum LB244R deposited as DSM32996 ; -Lactobacillus paracasei LB116R deposited as DSM32908; -Enterococcus faecium LB276R deposited as DSM32997 ; -Lactobacillus plantarum LB316R deposited as DSM33091 ; -Leuconostok mesenteriodes LB341R; - Deposited as DSM33093: Leuconostok mesenteriodes LB34 9R; -Lactobacillus plantarum LB356R deposited as DSM33094 ; -Lactobacillus plantarum LB312R deposited as DSM33098 ; For one of the bacterial strains selected from the group consisting of, for example, at least 97%, At least 96%, for example, at least 98%, at least 99% At least 99.5%, such as 9.8%, or at least 99% such as 100% (same). It can be 0.9%.

[0030] In embodiments of the present invention, genetic homology is -Deposited as DSM32906: Weissera viridecens LB10G; -Lactobacillus paracasei LB113R deposited as DSM32907; -Lactobacillus plantarum LB244R deposited as DSM32996 ; -Lactobacillus paracasei LB116R deposited as DSM32908; -Enterococcus faecium LB276R deposited as DSM32997 ; -Lactobacillus plantarum LB316R deposited as DSM33091 ; - Deposited as DSM33093: Leuconostok mesenteriodes LB34 9R, -Lactobacillus plantarum LB356R deposited as DSM33094 ; -Lactobacillus plantarum LB312R deposited as DSM33098 ; For one of the bacterial strains selected from the group consisting of, for example, at least 97%, At least 96%, for example, at least 98%, at least 99% At least 99.5%, such as 9.8%, or at least 99% such as 100% (same). It can be 0.9%.

[0031] Therefore, preferred embodiments of the present invention are -Deposited as DSM32906: Weissera viridecens LB10G; -Lactobacillus paracasei LB113R deposited as DSM32907; -Lactobacillus plantarum LB244R deposited as DSM32996 ; -Lactobacillus paracasei LB116R deposited as DSM32908; -Enterococcus faecium LB276R deposited as DSM32997 ; -Lactobacillus plantarum LB316R deposited as DSM33091 ; -Leuconostok mesenteriodes LB341R; - Deposited as DSM33093: Leuconostok mesenteriodes LB34 9R; -Lactobacillus plantarum LB356R deposited as DSM33094 ; -Lactobacillus plantarum LB312R deposited as DSM33098 ; You may choose from the group consisting of the following.

[0032] Therefore, in this further preferred embodiment of the present invention, the bacterial strain is -Deposited as DSM32906: Weissera viridecens LB10G; -Lactobacillus paracasei LB113R deposited as DSM32907; -Lactobacillus plantarum LB244R deposited as DSM32996 ; -Lactobacillus paracasei LB116R deposited as DSM32908; -Enterococcus faecium LB276R deposited as DSM32997 ; -Lactobacillus plantarum LB316R deposited as DSM33091 ; - Deposited as DSM33093: Leuconostok mesenteriodes LB34 9R; -Lactobacillus plantarum LB356R deposited as DSM33094 ; -Lactobacillus plantarum LB312R deposited as DSM33098 ; You may choose from the group consisting of the following.

[0033] The effect of the bacterial strain (and / or composition) according to the present invention on pathogenic microorganisms is significant. ru.

[0034] One embodiment of the present invention involves co-culturing methicillin-resistant Staphylococcus aureus (MRSA). The growth of Staphylococcus aureus, for example, is reduced by at least 20%, such as at least 30%. For example, a reduction of at least 50%, or at least 60%, or at least 40%. It can be made to happen.

[0035] In a preferred embodiment, the bacterial strain according to the present invention may be an isolated bacterial strain.

[0036] The present invention relates to each other through functional relationships in order to form a uniform concept according to the present invention. Microorganisms that share characteristics and / or effects, namely Staphylococcus aureus These include substances that inhibit the growth of pathogenic microorganisms and / or are associated with skin diseases. Microorganisms that reduce the colony formation level of pathogenic microorganisms such as Staphylococcus This document discloses the following: These lactic acid bacteria include, in particular, the German Collection for Deposited in Microorganisms and Cell Cultures The newly isolated microorganisms below, namely, -Deposited as DSM32906: Weissera viridecens LB10G; -Lactobacillus paracasei LB113R deposited as DSM32907; -Lactobacillus plantarum LB244R deposited as DSM32996 ; -Lactobacillus paracasei LB116R deposited as DSM32908; -Enterococcus faecium LB276R deposited as DSM32997 ; -Lactobacillus plantarum LB316R deposited as DSM33091 ; - Deposited as DSM33093: Leuconostok mesenteriodes LB34 9R; -Lactobacillus plantarum LB356R deposited as DSM33094 ; -Lactobacillus plantarum LB312R deposited as DSM33098 ; Microorganisms or their analogues, fragments, lysates, derivatives, and mutants selected from the group including the above. Or a combination of these.

[0037] The present invention relates to a composition comprising at least one of these new lactic acid bacteria, and also to a composition comprising This includes any combination of their strains and their analogues, fragments, lysates, derivatives, and mutants. It includes the composition.

[0038] The inventors of this invention have found that the method involves administration into the digestive tract of mammals and / or onto the skin of mammals. The treatment of one or more species or strains within a carrier is acceptable as a pharmaceutical suitable for local administration to the mucous membrane. A therapeutic composition for treating or preventing an infectious disease, comprising an effective concentration, wherein the provider The Otix strain exhibits characteristics related to pathogen growth, colony formation rate, and initial pathogen attachment to infection sites. The present invention provides a therapeutic composition having the ability to inhibit [a certain condition].

[0039] Therefore, a preferred embodiment of the present invention is a set comprising one or more bacterial strains according to the present invention. Regarding finished products.

[0040] The concentration of bacterial strains, preferably one or more viable strains and / or one or more dead strains, is , 10 5 ~10 13 The range of colony-forming units (CFUs), for example, 10 9 ~10 11 CF U range etc., 10 7 ~10 12 10 CFU scope etc. 3 ~10 14 Within the scope of CFU It is possible.

[0041] Bacterial strains, preferably one or more dead / inactivated strains, one or more strains, one or more elutes The concentration of the solution, one or more strain metabolites, ranges from 0.001% (w / w) to 20% (w / w). It can be a degree.

[0042] In the context of the present invention, the bacterial strains defined herein are dead bacterial strains that are subject to the present invention. It may be provided in a composition. The dead bacterial strain may be the whole dead cell or obtained from the dead cell. It may be provided as a solution, metabolite, derivative, analog, fraction, or extract.

[0043] In a further embodiment of the present invention, one or more of the bacterial strains are one or more viable strains , one or more dead or inactivated strains, one or more strain lysates, one or more strain metabolites, These can be offered as combinations of these.

[0044] In this composition, the bacterial strain according to the present invention includes one or more viable strains and one or more dead strains. or inactivated strain, lysates of one or more strains, metabolites of one or more strains, analogs, one As the above fragments, one or more derivatives, one or more mutants, or combinations thereof One or more lysates (such as those obtained from bacterial strains according to the present invention) may be provided. The strain metabolite, one or more analogues, one or more fragments, one or more derivatives, one or more mutants The variants or combinations thereof contain at least one pathogenic microorganism, such as MRSA. Its growth can be treated, mitigated, inhibited, prevented, and / or prevented.

[0045] In embodiments of the present invention, where the composition may be a topical composition, an oral composition, or a rectal composition, Preferably, the composition is a topical composition.

[0046] The compositions according to the present invention preferably include vehicles that are pharmaceutically or cosmetically acceptable. or may include excipients. In one embodiment of the present invention, the composition is available in solid, liquid, and viscous forms. It may be supplied in liquid form, emulsion, or dry form.

[0047] Oral consumption compositions are preferably pastes, soft gelatin capsules, and hard gelatin capsules. Capsules, powders, talc preparations, granules, beads, scented tablets, effervescent tablets, lozenges, buccal tablets Drugs, chewable tablets, sublingual tablets, oils, liquids, solutions, tinctures, emulsions, juices, concentrated Shrimp, syrup, spray, mist, drinking ampoules, gel, gum, tablets, coating It can be formulated as a pill, or as a food, feed product, or beverage.

[0048] In one embodiment of the present invention, the composition is used topically for the skin of either humans or animals. It may be a composition. Compositions for topical application are preferably pastes, talc, lotions, etc. It can be formulated into a custard, foam, cream, or ointment.

[0049] In one embodiment of the present invention, the local composition is magnesium hydrated silicate (talc) and the present invention It may be a powder composition comprising at least one of the bacterial strains.

[0050] In a further embodiment of the present invention, the powder composition for topical application is magnesium hydrate silicate. Nesium, at least one carbohydrate, and at least one of the bacterial strains of the present invention, It may be a powder composition containing the following:

[0051] In preferred embodiments, the topical composition includes lotion, custard, foam, cream, Alternatively, it may be formulated as an ointment, oil, or emulsion.

[0052] In a preferred embodiment, the treatment involves a topical composition containing the bacterial strain according to the present invention and an oral composition This is a combined treatment of both methods.

[0053] The composition, in addition to the bacterial strain according to the present invention, contains other probiotics and prebiotics. It further contains custard, antibacterial agents, antibiotics or other active antimicrobial substances, and / or Preferably selected from antioxidants, vitamins, coenzymes, fatty acids, amino acids, and cofactors. It may also contain one or more of the following substances:

[0054] In another embodiment of the present invention, the bacterial strain according to the present invention may be combined with the following: • A therapeutically effective dose of antibiotic. Either as a concomitant treatment or after antibiotic therapy. Therapeutic concentrations of antibiotics, including but not limited to: fusidic acid, vancomycete N, gentamicin, oxacillin, tetracycline, nitroflurantin, chlor Mufenicol, clindamycin, trimethoprim-sulfamethoxazole, cepha Members of the rosporin antibiotic family (e.g., cefaclor, cefadroxil, Cefixime, cefprodil, ceftriaxone, cefuroxime, cephalexin, Lorra (e.g., Calbef), members of the penicillin family of antibiotics (e.g., ampicillin, Amoxicillin / Clavilanate, Bacampicillin, Cloxicillin, Penicillin VK (For example, members of the fluoroquinolone family of antibiotics, such as ciprofloxacin) , grepafloxacin, levofloxacin, lomefloxacin, norfloxacin, off (e.g., roxacin, sparfloxacin, trovafloxacin), and; or macrolides Members of the antibiotic family (e.g., azithromycin, erythromycin, etc.), • A therapeutically effective dose of anti-inflammatory drugs. Either as a co-treatment or after therapy, and / or teeth • Anti-inflammatory drugs at therapeutic concentrations.

[0055] In one embodiment of the present invention, the composition is a pharmaceutical, veterinary drug, food, or nutritional supplement. It may be a food or a nutritional supplement composition. The composition (preferably for oral administration) is preferred In addition, one or more thickeners and / or one or more sweeteners and / or one or more It may contain artificial sweeteners, and the thickener is preferably cellulose ether, xanthan gum Ingredients: gelatin, highly dispersed silicon dioxide, starch, carragenan, Arginate, tragacanth, agar, gum arabic, pectin, and polyvinyl esters A polysaccharide selected from the group including glucose, fructose, and sucrose, which are used as sweeteners. S, glucose syrup, sorbitol, mannitol, xylitol, maltitol, Stewia, saccharin, sodium cyclamate, acesulfame potassium Selected from the group including and / or aspartame.

[0056] Preferred foods and nutritional supplements in the sense of the present invention are effervescent tablets and vitamin tablets. Dietary supplements, mineral tablets, trace element tablets, beverage powders, beverages, juices, milk drinks Food, yogurt, mineral water, still water, bonbons, chewable tablets, juice This may include syrups, coated pills and lozenges, and aerosols. .

[0057] Furthermore, the composition also contains builders, enzymes, electrolytes, pH adjusters, thickeners, and prebiotics. Tixes, fluorescent agents, graying inhibitors, pigment transfer inhibitors, foam regulators and / or colorants. It may also contain other agents.

[0058] Prior art addresses the pathogenicity of Staphylococcus aureus (suppositories) in skin diseases, such as MRSA. The use of probiotic strains to prevent or treat bacterial infections is disclosed. There is nowhere to be found.

[0059] It is truly remarkable that we were able to identify a group of lactic acid bacteria that share the same advantageous characteristics. This was the case. Bacteria, especially lactic acid bacteria, are non-pathogenic, yet they can be found in the skin or microbiome. Without causing any significant damage or impact, pathogenic microorganisms These properties are not combined to treat, alleviate, suppress, prevent, and / or prevent the growth. stomach.

[0060] In the following, preferred embodiments relating to one broad aspect of the present invention are described above. It will be understood that this is equally applicable to each of the other broad embodiments of the present invention described herein. Unless otherwise indicated by the context, preferred embodiments described later can be combined. This will be further understood. When used herein, the term local means the surface of the body (e.g., This includes references to formulations suitable for application to the skin or mucous membranes. Mucous membranes include the vagina, penis, urethra, bladder, anus, and mouth (cheeks, soft palate, underside of the tongue, and floor of the mouth). (including), nose, throat (including the mucous membranes of the pharynx, larynx, trachea and esophagus), bronchi, lungs, eyes and It includes the mucous membrane of the ear.

[0061] One embodiment of the present invention treats, mitigates, inhibits, prevents, and / or treats the growth of pathogenic microorganisms. This relates to compositions according to the present invention for use in preventing

[0062] More preferably, the present invention relates to a composition comprising one or more pathogenic bacterial infections in mammals. For use in treatment, mitigation, suppression, and prevention, it may provide as defined herein. .

[0063] More preferably, the present invention provides a composition for use in preventing the growth of pathogenic microorganisms. Therefore, it may provide what is defined herein.

[0064] The bacterial infection may preferably be a staphylococcal infection in mammals.

[0065] Staphylococcal infection may preferably be MRSA infection.

[0066] One embodiment of the present invention is for dermatitis, atopic dermatitis, eczema, carbuncles, cellulitis, rosacea, psoriasis, Treatment of diseases resulting from Staphylococcal infection, such as diaper rash, impetigo, or wounds. Compositions defined herein for use in placement, mitigation, suppression, and / or prevention Related to objects.

[0067] In further embodiments of the present invention, the composition is used for atopic dermatitis, eczema, impetigo, and burns. or caused by Staphylococcus aureus, including skin infections related to diaper rash. Bacterial strains (or their lysates, metabolites, derivatives) for treating skin infections that may occur. It contains at least one of the following: analog, fraction, or extract.

[0068] Burn patients are typically given antibiotics to reduce the incidence of opportunistic infections. St. saccharomyces are often associated with infections of severe burns. For this reason, ointments and lotions are used. The following are beneficial compositions or lysates obtained from the bacterial strain of the present invention, including talc, gel, etc., and metabolic compounds. Products, derivatives, analogs, fractions, or extracts may be combined to achieve inhibition of skin pathogens. Furthermore, it may be effective in preventing the growth of pathogens on the patient's skin.

[0069] Another example is the use of antibiotics in livestock, and the compositions disclosed in this invention are pathogens It may be administered to the skin or mucous membranes of mammals to reduce colonization.

[0070] A preferred embodiment of the invention is used for the prevention or medical treatment of staphylococcal infections. This relates to a composition for the purpose of [doing something].

[0071] The microorganisms are advantageously present in the composition in a viable form or in a killed / dead form. The bacterial strain may be encapsulated, microencapsulated, spray-dried, and / or freeze-dried. It can be provided in the following form. Furthermore, the bacterial strain can be provided in the form of a cell lysate, metabolite, derivative, analog , fraction or extract.

[0072] In one embodiment of the present invention, the bacterial strain is present in the composition in an amount of 0.001% to 20% by weight, preferably 0 .005% to 10% by weight, particularly preferably 0.01% to 5% by weight. It may be present in.

[0073] A preferred embodiment of the present invention is approximately 1×10 per day 3 ~1×10 14 CFU of viable bacteria, more preferably approximately 1×10 per day 4 ~l×10 10 , most preferably approximately about 5×10 per day 4 ~1×10 9 CFU of viable bacteria. When the condition to be treated includes antibiotic-resistant pathogens and the patient is an adult, a typical dosage is approximately 1×10 per day ~1×10 2 ~1×10 14 CFU of viable bacteria, preferably about 1×10 per day 8 ~1×10 10 , more preferably approximately 2.5×10 8 ~1×10 10 CFU of viable bacteria. When the subject to be treated is an infant over 6 months old age, the dosage is typically 1×10 per day 6 ~1×10 9 C FU of viable bacteria.

[0074] The antibiotic-resistant bacteria, which is a further aspect of the present invention, are the following antibiotics, namely, fici nate, vancomycin, metronidazole, methicillin and / or fidaxomicin It is resistant to at least one of the following.

[0075] The present invention relates to novel bacterial strains, and the general references in the claims refer to living cells, dead cells. Killed / destroyed cells and their lysates, metabolites, derivatives, analogues, fractions, or extracts , as well as such living cells, dead / killed cells and their lysates, metabolites, inducers The present invention relates to compositions comprising conductors, analogues, fractions, or extracts.

[0076] The composition according to the present invention is suitable for infants, toddlers, children, healthy individuals, the elderly, immunosuppressed individuals, and yellow grapes. Individuals with a single or recurrent coccal infection and / or antibiotic-resistant bacterial infection In infected individuals, the growth of pathogenic microorganisms such as MRSA is treated, mitigated, suppressed, and prevented. And / or may be suitable for preventing.

[0077] In one embodiment of the present invention, the composition according to the present invention is used for animals including pets and livestock. To treat, mitigate, suppress, prevent, and / or treat the growth of pathogenic microorganisms such as MRSA in materials. It may be suitable for prevention.

[0078] Therefore, the composition of the present invention is a pharmaceutical product that is beneficial for treating or preventing the growth of Staphylococcus aureus. It can be used to prepare a. In one embodiment of the present invention, the composition is, for example, proba Combined with iotics compositions and / or prebiotic compositions, for therapeutic purposes It may be used for preventative purposes.

[0079] The combination of the composition according to the present invention and the probiotic strain promotes the growth of Staphylococcus aureus. By reducing the growth by at least 50% compared to growth without the bacterial strain, co-culture This provides a combined composition that can inhibit the growth of Staphylococcus aureus. Here, growth is measured as the colony-forming unit during the stationary growth phase of Staphylococcus aureus. .

[0080] In one embodiment of the present invention, the bacterial strain defined herein is the only one present in the composition. It may be a bacterium. A composition comprising only the bacterial strains defined herein is not available without the bacterial strains. Compared to growth, it shows at least a 50% reduction in the growth of Staphylococcus aureus.

[0081] The "decrease" in growth was "statistically significant" compared to the growth period in the absence of the bacterial strain of the present invention. " and 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11% 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25% 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75% This may include a decrease of 80%, 85%, 90%, 95%, or 100%.

[0082] In one embodiment of the present invention, growth inhibition is defined as a reduction of at least 25% in growth. It can be determined. Preferably, growth inhibition is determined as a reduction of at least 50% in growth. More preferably, the growth inhibition is a reduction of at least 90% in growth. It will be decided.

[0083] The "decrease" in the number of microorganisms is compared to the number of CFU / ml in the absence of the bacterial strain of the present invention. The comparison can be "statistically significant" at 10%, 15%, 20%, 25%, 30%, and 35%. 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, This may include a decline of 90%, 95%, 97%, 99%, 99.9%, or 100%.

[0084] The number of microorganisms is measured as colony-forming units (CFU / ml).

[0085] The microorganisms according to the present invention may preferably be in an isolated or purified form. Here, the term "isolated" specifically refers to lactic acid bacteria that, for example, are isolated from the natural culture medium of the lactic acid bacteria. It means derived from a damp culture medium. The term "purified" refers to absolute purity. Not restricted by.

[0086] In one embodiment of the present invention, the probiotic strain is a stabilized form of a bioisolated microorganism and It can be used as follows. Suitable stabilization methods are known to those skilled in the art, and different freeze protectants can be used. Including freeze-drying or freeze-drying (lyophiliza (including tion).

[0087] In further embodiments of the present invention, the strain may be used as a bioisolated strain.

[0088] Preferably, the strain can be used as a live isolated and stabilized strain. More preferably, The strain can be used as a live isolated strain stabilized by freeze-drying. More preferably The strain can be stabilized by freeze-drying and used as a live isolate containing a cryoprotectant.

[0089] The present invention relates to viable and / or dead (killed) bacterial strains. Both embodiments may fall within the scope of the present invention.

[0090] Suitable methods for extermination (e.g., biological, chemical, or physical extermination methods) are: This is well known to those skilled in the art. However, in this case, the bacterial strain is also freeze-dried. It can also be used in a dry form. The form of microbial killing is fermentation broth and any existing metabolic It may include products.

[0091] The terms "killed" or "dead" refer to a state where cell division is impossible and, moreover, This relates to inactivated lactic acid bacteria that do not possess metabolic activity. Dead or killed lactic acid bacteria remain intact. They may have ruptured cell membranes.

[0092] "Soluble," "derivative," "analog," "fraction," or "extract" is dead or These can be obtained from sterilized lactic acid bacteria. Lysates, fractions, derivatives, analogues, and extracts. Preferably, this reduces the movement of pathogenic microorganisms between the surface of the first target and the surface of the second target. It has properties that cause a decrease, and here the terms “solubil” and “extract” are used in particular in aqueous media. This refers to a solution or suspension of microbial cells according to the present invention in the body, such as DNA, RNA, etc. It includes macromolecules such as proteins, peptides, lipids, and carbohydrates, as well as cell debris. The lysate preferably contains the cell wall, or cell wall components including binding receptors. The method for producing the dissolved product is well known to those skilled in the art, for example, "French Press Start by using a ball mill with "res" or enzymatic dissolution, glass beads, or iron beads. The goal is to destroy the cells by enzymatic, physical, or chemical methods. Examples of enzymatic cell lysis include individual enzymes and enzyme cocktails, such as proteases. Proteinase K, lipase, glycosidase, and other enzymes may be involved, and chemical dissolution is possible with ions. It can be induced by surfactants such as HOA and SDS, acids or bases, and physical methods are also available. Using high pressure such as a French press, volumetric molar osmotic pressure concentration, temperature, or alternating heating and cooling. It can also be carried out by using chemical methods, physical methods and Enzymatic methods can, of course, be combined with this.

[0093] In preferred embodiments, the composition and / or bacterial strain according to the present invention is used in mammals. It is suitable for treating, alleviating, controlling, and preventing diseases associated with pathogenic microbial infections.

[0094] In one embodiment, the disease is psoriasis, atopic dermatitis, carbuncle, cellulitis, rosacea, dry skin. Skin, allergies, eczema, rash, UV-sensitive skin, detergent-sensitive skin (detergent odor) The irritation is caused by the enzymes used and by sodium lauryl sulfate. Staphylococcus aureus, including (and others), including thinned skin (e.g., skin of the elderly and children) A group of skin diseases susceptible to infection may be selected.

[0095] The present invention also relates to a method for reducing the number of Staphylococcus bacteria on the skin of patients with atopic dermatitis. do.

[0096] In one embodiment of the present invention, a composition comprising at least one bacterial strain is used to treat inflammatory skin The number of Staphylococcus aureus bacteria on the skin of patients with skin diseases is used to determine if the Staphylococcus aureus bacteria result in a skin infection. It can be controlled to a level that does not cause harm.

[0097] In a further embodiment of the present invention, a composition comprising at least one bacterial strain is used to yellow The level of Staphylococcus aureus is approximately 10. 5 CFU / 1cm of skin 3 Inflammatory skin diseases less than The number of Staphylococcus aureus bacteria on the patient's skin can be controlled.

[0098] In this specification, terms such as "about" or "approximately" are used in the present invention. In all descriptions of the range that can be obtained, the exact numerical range is given as "approximately" or "about (approximately)". It is necessary to express it with expressions such as "ox.)" or "approximately". It is not necessary, but even slight deviations above or below the numbers shown still constitute the present invention. It will be obvious to those skilled in the art that it is within the range. In one embodiment of the present invention, a small deviation This includes deviations of 4% or less, such as deviations of 2% or less, or deviations of 3% or less, such as deviations of 1% or less. This may include deviations of 5% or less, such as the deviation shown.

[0099] In one embodiment of the present invention, one or more biologically pure cultures of the bacterial strains of the present invention It may be provided.

[0100] In this context, the term "mammal" includes humans, primates, domesticated animals, competitive animals, and rodents. and may include pets. Non-human animal examples include mice, rats, and hamsters. Rodents such as turtles and guinea pigs, rabbits, dogs, cats, sheep, pigs, piglets, female piglets Poultry, turkeys, broilers, mink, goats, cattle, horses, and great apes This includes non-human primates such as monkeys.

[0101] The term "effective dose" can be dependent on the context in which it is applied. Administer a composition to reduce the risk, and / or the severity of the staphylococcal infection. Administer a composition to reduce the amount of Staphylococcus aureus in the subject. In the context of reducing the risk, an effective amount of the composition described herein is used to treat staphylococcal infections. and / or induce remission, and reduce the severity of staphylococcal infections and / or In an amount sufficient to reduce the transmission of Staphylococcus aureus between subjects and / or the likelihood of such infection. Yes. A decrease in the amount of Staphylococcus aureus in the subject indicates a decrease in the severity or infection of staphylococcal infection. A 10% decrease, a 20% decrease, a 30% decrease, a 40% decrease, and a 50% decrease in likelihood. , a 60% decrease, a 70% decrease, an 80% decrease, a 90% decrease, a 95% decrease, a 98% decrease It could be a decrease, a 99% decrease, or a 99.9% decrease.

[0102] An effective dose may be administered as a composition in one or more doses.

[0103] An effective dose of the composition is administered as a topical, oral, or combination thereof. This can be done, preferably as a local administration.

[0104] The composition can be administered by administering two or more types of mammalian feed or food, It may be applied to the nose and / or skin and / or as a nasal spray.

[0105] In one embodiment of the present invention, the composition comprises at least one bacterial strain and preva This includes iotics.

[0106] "Prebiotics" are indigestible food components that enhance the growth of specific microorganisms. "Synbiotics" are defined as at least one probiotic and at least one This composition contains prebiotics for beneficial bacteria (e.g., It is understood that it encourages the growth of (probiotics). Therefore, a potent SymBio Tics combines specific strains of probiotic bacteria with carefully selected prebiotics. It is based on a combination with [another substance]. This synbiotic is important for the health of mammals. It could potentially lead to health benefits.

[0107] According to another aspect of the present invention, probiotic microorganisms and at least one further effective A probiotic composition containing the ingredients is provided.

[0108] Prebiotics are symbiotic microorganisms (e.g., bacteria) that contribute to the health of their host. Prebiotics refer to chemical products that induce the growth and / or activity of (and fungi). These are microorganisms that pass through the upper digestive tract undigested and form colonies on microorganisms in the large intestine or skin. It is an indigestible carbohydrate that stimulates the growth and / or activity of beneficial bacteria.

[0109] Some oligosaccharides used as prebiotics are fructooligosaccharides (FO S), xylooligosaccharide (XOS), polydextrose, pectin, galactooligosaccharide ( It is either GOS (Glycosaccharide Oxide) or human milk oligosaccharide (HMO). In addition, it is a disaccharide such as lactulose. Alternatively, some monosaccharides such as lactose or tagatose can also be used as prebiotics. It can be used in this way.

[0110] In one embodiment of the present invention, at least one prebiotic compound is part of the composition of the present invention. It can be contained in substances. In a very broad sense, prebiotics are probiotics. These are all compounds that can be metabolized by S.

[0111] Preferably, the prebiotics are indigestible or difficult to digest by mammals. It is morphogenic. Therefore, after being taken up by mammals, it becomes an indigestible prebiotic. It passes through the small intestine and enters the large intestine, where it stimulates the growth of probiotics. Therefore, prebiotics are a food source for probiotics. They can serve this purpose. Prebiotics are mostly indigestible carbohydrates. It is thought that probiotics promote growth. Prebiotics are, for example, For example, cabbage, onions, whole grains, bananas, garlic, honey, chives, archicho Naturally found in cereals, fortified foods and beverages, and dietary supplements. Biotics are well known in the art, and when used in the present invention, prebiotics There are no particular restrictions on the S itself.

[0112] However, in one embodiment, at least one prebiotic in the composition The product is selected from the following compounds and compositions: namely, indigestible carbohydrates, β -Glucan, mannan oligosaccharide, inulin, oligofructose, human milk oligosaccharide (HM O), galactooligosaccharide (GOS), lactulose, lactosucrose, galactotrio Fructooligosaccharides (FOS), cellobiose, cellodextrin, cyclodextrin Phosphorus, maltitol, lactitol, glycosylsucrose, betaine, vitamin E, This is a variant of it (this variant contains alpha-tocopherol, beta-tocopherol, and Tocopherol, delta-tocopherol, tocotrienol, and tocomonoenol (Selected from). In some cases, mannan oligosaccharides and / or inulin are preferred. There are HMOs such as lacto-N-tetraose, lacto-N-fucopentaose, and Cthut-N-triose, 3'-sialyl lactose, lacto-N-neofocopentaose sialic acid, L-fucose, 2-fucosyl lactose, 6'-sialyl lactose, lact This may include to-N-neotetraose and 3'-fucosyl lactose.

[0113] Prebiotics may also be used in the topical compositions of the present invention.

[0114] In one embodiment, at least one of the following prebiotic compounds is the present invention. It is used in topical compositions, namely lactose, β-glucan, and mannan oligosaccharides. Inulin, oligofructose, galactooligosaccharide (GOS), lactulose, lact Sucrose, galactotrioose, fructooligosaccharide (FOS), cellobiose, cellodiol Chistrin, cyclodextrin, maltitol, lactitol, glycosylsucrose , betaine, vitamin E or its variants (the variants are alpha-tocopherol, ba Tocopherol, gamma tocopherol, delta tocopherol, tocotrienol (Selected from tocomonoenols), lacto-N-tetraose, lacto-N-fuco Pentaose, lacto-N-triose, 3'-sialyl lactose, lacto-N-neo Fucopentaose, sialic acid, 2-fucosyl lactose, 6'-sialyl lactose, These are kuto-N-neotetraose and 3-fucosyl lactose. In some cases, lacto - and / or mannan oligosaccharides and / or inulin may be preferred.

[0115] D-fucose and L-fucose enhance the skin's natural defenses and stimulate epidermal immune defense. , and / or to prevent and / or treat autoimmune diseases of the skin. One embodiment of the present invention. In an embodiment, the composition contains D-fucose or L-fucose.

[0116] In one embodiment of the present invention, the composition further contains L-fucose at a concentration of 10 mM to 500 mM in the composition. In an embodiment, the composition contains L-fucose at a concentration of 10 mM to 500 mM in the composition.

[0117] According to still further features of the described preferred embodiments, the composition further contains at least one active ingredient. In an embodiment, the composition contains at least one active ingredient.

[0118] In one embodiment of the present invention, the composition contains at least one bacterial strain of the present invention in combination with at least one additional probiotic microorganism selected from the group consisting of another bacterium, yeast or mold. In one embodiment of the present invention, the composition contains at least one bacterial strain of the present invention in combination with at least one additional probiotic microorganism selected from the group consisting of another bacterium, yeast or mold. In one embodiment of the present invention, the composition contains at least one bacterial strain of the present invention in combination with at least one additional probiotic microorganism selected from the group consisting of another bacterium, yeast or mold.

[0119] The composition according to the present invention may contain at least one bacterial strain in combination with at least one additional probiotic microorganism, wherein the at least one additional probiotic microorganism may be selected from, but is not limited to, the following. That is, The composition according to the present invention may contain at least one bacterial strain in combination with at least one additional probiotic microorganism, wherein the at least one additional probiotic microorganism may be selected from, but is not limited to, the following. That is, The composition according to the present invention may contain at least one bacterial strain in combination with at least one additional probiotic microorganism, wherein the at least one additional probiotic microorganism may be selected from, but is not limited to, the following. That is, Bifidobacterium lactis DSM10140, Bifidobacterium lactis LKM512, Bifidobacterium lactis DSM20451, Bifidobacterium bifidum BB-225, Bifidobacterium adolescentis BB-102, Bifidobacterium breve BB-308, manufactured by the Japan Bifidobacterium Center (Japan Bifidobacterium Center) DSM10140, Bifidobacterium lactis LKM512, Bifidobacterium lactis DSM20451, Bifidobacterium bifidum BB-225, Bifidobacterium adolescentis BB-102, Bifidobacterium breve BB-308, manufactured by the Japan Bifidobacterium Center (Japan Bifidobacterium Center) DSM10140, Bifidobacterium lactis LKM512, Bifidobacterium lactis DSM20451, Bifidobacterium bifidum BB-225, Bifidobacterium adolescentis BB-102, Bifidobacterium breve BB-308, manufactured by the Japan Bifidobacterium Center (Japan Bifidobacterium Center) DSM10140, Bifidobacterium lactis LKM512, Bifidobacterium lactis DSM20451, Bifidobacterium bifidum BB-225, Bifidobacterium adolescentis BB-102, Bifidobacterium breve BB-308, manufactured by the Japan Bifidobacterium Center (Japan Bifidobacterium Center) DSM10140, Bifidobacterium lactis LKM512, Bifidobacterium lactis DSM20451, Bifidobacterium bifidum BB-225, Bifidobacterium adolescentis BB-102, Bifidobacterium breve BB-308, manufactured by the Japan Bifidobacterium Center (Japan Bifidobacterium Center) DSM10140, Bifidobacterium lactis LKM512, Bifidobacterium lactis DSM20451, Bifidobacterium bifidum BB-225, Bifidobacterium adolescentis BB-102, Bifidobacterium breve BB-308, manufactured by the Japan Bifidobacterium Center (Japan Bifidobacterium Center) Bifidobacterium longum B B-536, Bifidobacterium NCI as described in European Patent No. 2823822 This is MB41675. Bifidobacterium bifidum BB-225, bifidobacterium Cterium adolescentis BB-102, Bifidobacterium breve BB- 308, available from DuPont Nutrition Biosciences ApS. Possible Bifidobacterium lactis HN019 (Howaru), Groupe Bifidobacterium lactis DN173010, available from Danone, Ch Bifidobacterium lactis Bb-12 available from r. Hansen A / S Available from DuPont Nutrition Biosciences ApS Bifidobacterium lactis 420, Bifidobacterium breve Bb-03 Bifidobacterium lactis BI-04, DuPont Nutrition Bifidobacterium lactis available from Biosciences ApS -07, Bifidobacterium bifidum Bb-02, Bifidobacterium bifidum Bifidobacterium Bb-06, Bifidobacterium longum KC-1 and Bifidobacterium Um Longum 913 (DuPont Nutrition Biosciences) ApS), Bifidobacterium breve M-16V (Morinaga) and / or Proba Lactobacillus having iotic effects, and being one of the following strains: In other words, Lactobacillus rhamnosus Lactobacillus acidophilus (Lac) LGG (Chr. Hansen), Lactobacillus acidophilus (Lac) tobacillus acidophilus)NCFM(DuPont Nutri tion Biosciences ApS), Lactobacillus bulgaricus (Lac tobacillus bulgaricus) 1260(DuPont Nutrit ion Biosciences ApS), Lactobacillus paracasei (Lacto bacillus paracasei)Lpc-37(DuPont Nutriti on Biosciences ApS), DuPont Nutrition Bio Lactobacillus rhamnosus HN001 (Ho waru), from DuPont Nutrition Biosciences ApS Available Streptococcus thermophilus Streptococcus thermophilus ST21, Tobacillus paracasei subspecies paracasei CRL431 (ATCC55544), Medi This is Lactobacillus paracasei strain F-19 manufactured by pharm, Inc. • Paracasei LAFTI L26 (DSM Food Specialties, Oran) (Da) and Lactobacillus paracasei CRL431 (Chr. Hansen), lact Bacillus acidophilus PTA-4797, Lactobacillus salivarius (Ls L. alivarius (Ls-33) and Lactobacillus curvatus (L. curv atus)853(DuPont Nutrition Biosciences Ap S) is Lactobacillus casei subspecies rhamnothus LC705 is a Finnish patent. This is described in Invention No. 92498 (Valio Oy), Lactobacillus DS M15527 (Bifodan), Lactobacillus DSM15526 (Bifodan) Lactobacillus rhamnosus GG (LGG) (ATCC53103) is a U.S. 5 It is described in issues 032 and 399, and Lactobacillus rhamnosus LC705 ( DSM7061), propionic acid bacteria, for example, Finnish Patent Invention No. 92498 Propionibacterium furo, which is described in more detail in (Valio Oy) Idenreich (Propionibacterium freudenreichii) Nitrosomonas subspecies shermanii PJS (DSM7067) Eutropha (Nitrosomonas eutropha) D23 (ABIome) Staphylococcus hominis A9 Stocks, C2 stocks, AMT2 stocks, AMT3 stocks, AMT4-C2 stocks, AMT4-Gl stocks, and / Alternatively, it is the AMT4-D12 strain. (All manufactured by Matrisys Bioscience) ), Staphylococcus epidermidis ermidis) M034 shares, M038 shares, All shares, AMT1 shares, AMT5-C5 shares, and / or AMT5-G6 strain (all from Matrisys Bioscience) Lactobacillus plantarum YUN-V2.0 (BCCM LMG P-29456) ), Lactobacillus pentosus (L. pentosus) YUN-V1.0 (BCC N LMG P-29455), Lactobacillus rhamnosus YUN-S1.0 (BCC M LMG P-2961) and / or any combination thereof.

[0120] In one embodiment of the present invention, the composition is lactic acid that can improve the integrity of the adhesion bond in combination with at least one strain selected from the group of bacteria, and at least one bacterial strain as defined herein is included.

[0121] In a further embodiment of the present invention, the composition is Lactobacillus rhamnosus LGG (C hr. Hansen), Lactobacillus acidophilus NCFM (DuPont), L actobacillus salivarius Ls-33 (DuPont), Propionibacterium jensenii P63 (Du Pont), Bifidobacterium lactis 420 (DuPont) and Lactoba cillus acidophilus La-14 (DuPont), and / or at least selected from the group consisting of cell lysates and / or soluble metabolites of the probiotic strains, and at least one bacterial strain as defined herein is included.

[0122] The composition according to the present invention suitable for oral ingestion may provide 1×10 6 to 1 [[ID=3l]] ×10 14 colony forming units (CFU) per serving or per dose.

[0123] [ [[ID=;38]]As used herein, and as well understood in the art, "treatment" is an approach to obtain beneficial or desired results including clinical results. For the purposes of this content, beneficial clinical results or desired clinical results include the alleviation or remission of one or more symptoms, reduction of the degree of the disease, stabilization of the disease (i.e., no worsening) ​Prevention of disease, delay or slowing of disease progression, and / or remission of the disease state. This includes, but is not limited to, mitigation.

[0124] This decrease is 10%, 20%, 30%, 40%, 50%, and 6% of the severity of complications or symptoms. The decrease could be 0%, 70%, 80%, 90%, 95%, 98%, or 99%.

[0125] One embodiment of the present invention may provide a method for treating the skin of a mammal. The method is The method involves administering a therapeutically effective dose of at least one bacterial strain to a subject requiring the method (e.g., a mammal). Administer and thereby treat the skin to colonize and / or carrier level and / or This includes reducing infection.

[0126] In a further embodiment of the present invention, skin colonization is suppressed by antibiotic-resistant microorganisms. It can be caused by MRSA. Skin colonization can be caused by MRSA.

[0127] The at least one bacterial strain proliferates in the digestive tract, nasal cavity, or skin of mammals and They may be able to form colonies.

[0128] The present invention may offer several advantages. In particular, it may be possible to produce antibiotic-resistant microbial species. Because of this, as long as the use of antibiotics has harmful effects, conventional antimicrobial agents will not be used. It is desirable to take action. For this reason, the present invention relates to the production of antibiotic-resistant pathogens of future generations. It does not contribute to life.

[0129] In one embodiment of the present invention, the effects of the composition and method according to the present invention are minimal. A rinsing process to remove biofilm from the surface before adding even one lactic acid bacterium. It does not include.

[0130] Deposit of biomaterials The following biological materials, microorganisms, are included in the German Collection for Deposited in Microorganisms and Cell Cultures That is to say, -Deposited as DSM32906: Weissera viridecens LB10G; -Lactobacillus paracasei LB113R deposited as DSM32907; -Lactobacillus plantarum LB244R deposited as DSM32996 ; -Lactobacillus paracasei LB116R deposited as DSM32908; -Enterococcus faecium LB276R deposited as DSM32997 ; -Lactobacillus plantarum LB316R deposited as DSM33091 ; - Deposited as DSM33093: Leuconostok mesenteriodes LB34 9R; -Lactobacillus plantarum LB356R deposited as DSM33094 ; -Lactobacillus plantarum LB312R deposited as DSM33098 ; That is the case.

[0131] The embodiments and features described in the context of one aspect of the present invention are also It should be noted that this invention also applies to other aspects of the present invention.

[0132] The present invention will now be described in more detail in the following non-limiting examples. [Examples]

[0133] Example 1: Strain Screening and Identification

[0134] sample A collection of Lactobacillus (LAB) strains was established for the identification and selection of bacterial strains according to the present invention. At least 995 Lactobacillus strains were isolated from samples of different origins, including homemade sauerkraut, kimchi, and healthy human donor samples (vagina, oral cavity, anus, skin). These samples were collected on Man Rogosa Sharp (MRS, Sigma-Aldrich) broth and agar and cultured anaerobically at 37°C overnight or until colony formation. The isolates were seeded and subcultured to obtain pure colonies. The pure colonies were stored in MRS broth containing 25% glycerol at -80°C for future use. 16S rRN A The strain was identified using the Sanger sequencing standard.

[0135] Example 2: Co-culture assay / competitive assay

[0136] The competition between bacterial strains and Staphylococcus aureus is described in the following publication, namely, Dowarah, R. ,et al.2018,Selection and characterizati on of probiotic lactic acid bacteria and its impact on growth,nutrient digestibid. lity, health and antioxidant status in us aned piglets, PLoS ONE,13(3), Khare, A.&Tav azoie, S. (2015), Multifactorial Competitio n and Resistance in a Two-Species Bacter ial System, PLoS Genetics, 11(12), 1-21) odor It was determined by the method described.

[0137] Staphylococcus aureus subspecies aureus COL (CCOS461), yellow bud Uococcus CC1 (Bispebjerg University Hospital,Cl ausen et al.(2017)Br.J.Dermatol.177:1394 -1400) (Doi 10.1111 / bjd.15470) and yellow grapes Cocci US300 (ATCC BAA-1717) were used as the test organism. Yellow grape Cocci were cultured in Brain Heart Infusion (BHI) broth. Yellow Staphylococcus CC1 is particularly associated with atopic dermatitis, and is found in patients suffering from atopic dermatitis. This is a clonal type associated with patients with the FLG mutation.

[0138] The cell density of overnight cultures of Staphylococcus aureus and bacterial strain isolates was measured using light at 600 nm. The density (OD600) was adjusted, and then centrifuged (at 6,000 rpm for 2 minutes). The cells were collected. The cell pellet was washed twice in phosphate buffer solution (1×PBS) and then 1×P Resuspend in BS. Mix 1 ml of each cell suspension in 50 mL of BHI broth. Then, co-incubate at 37°C for 24 hours to obtain single cultures of each Staphylococcus aureus and each LAB. Use the sample as a control. At 0, 2 hours, 6 hours, 10 hours, and 24 hours, the cell solution The serial dilutions are seeded onto nutrient agar plates and the formed colonies are counted. Used for LAB isolated strains, mannitol salt phenol red agar (Sigma-Aldri (ch) was used against Staphylococcus aureus.

[0139] Lactobacillus rhamnosus LGG (Chr. Hansen) was used in all experiments. This was used as a control probiotic strain.

[0140] Twenty-two strains of Lactobacillus (LAB) derived from a collection of 675 bacterial strains improved the growth of the test strains. Three tested Staphylococcus aureus strains were determined to have the ability to reduce the strain by at least 25%. They were identified as being able to overcome all growth. Eight bacterial strains grew by more than 90%. It was determined to reduce Lactobacillus rhamnosus LGG. It couldn't even overcome the growth of the cocci.

[0141] Example 3 Co-aggregation

[0142] Co-aggregation is a known method, Cisar, JO et al. (1979), "Sp ecificity of Coaggregation Reactions bet ween Human Oral Streptococci and Strains of Actinomyces Viscosus or Actinomyces Infection and Immunity 24(3) Determined by :742-52.

[0143] All bacterial strains were grown in MRS broth, and Staphylococcus aureus strains were grown in BHI broth. The cells were grown overnight in a container at 37°C. The cell samples after one night were centrifuged (at 6000 rpm). The pellet was collected after 2 minutes and the supernatant was removed from the pellet. The pellet was then placed in 1×PBS buffer. Wash it twice.

[0144] Resuspend the cell pellet in 1×PBS and add 500 μl of Staphylococcus aureus and bacterial strains. The solution was dispensed into a 24-well plate. The plate was then incubated on a shaker (200 rpm). The bait was used to observe the formation of self-aggregation and co-aggregation at 1 hour, 2 hours, 3 hours, and 24 hours. We will observe it visually later.

[0145] As a control for autoaggregation, samples of Staphylococcus aureus and bacterial strains were treated with PBS buffer 7. It was mixed with 50 µl of buffer, resulting in a final volume of 1500 µl in each well.

[0146] The plate was incubated on a shaker at approximately 200 rpm for 24 hours. Cluster formation will be observed at 1 hour, 2 hours, 3 hours, and 24 hours.

[0147] The formation of coagulation was visually assessed on a scale of 1 to 5 using the following criteria. 1: No aggregation 2: Initial aggregation by visual inspection 3: Formation of aggregates smaller than 0.5 mm 4: Formation of aggregates larger than 0.5 mm and smaller than 1 mm Formation of aggregates larger than 5.1 mm

[0148] [Table 1]

[0149] Example 4: Spot-on-lawn assay

[0150] Zhang P.et al.(2015)Interstrain interac tions between bacteria isolated from vac uum-packaged refrigerated beef、Appl Envi ron Microbiol 81:2753-2761.doi:10.1128 / A EM.03933-14, and Arena, MP et al. (2016) Use of Lactobacillus plantarum Strains as a Bio-Control Strategy against Food-Borne Pathogenic Microorganisms、Frontiers in Microbiology 7(APR):1-10.https: / / doi.org Using the method described at / 10.3389 / fmicb.2016.00464 Spot-on-loan studies were conducted for growth inhibition and antimicrobial metabolites.

[0151] The bacterial strain isolated from Example 1 was taken from the stored sample in 2 mL of MRS in a 24-well plate. The strain was cultured in broth. The Staphylococcus aureus strain was placed in approximately 200 mL of Erlenmeyer flask. The LAB isolate was cultured in BHI culture medium. The LAB isolate and Staphylococcus aureus solution were incubated overnight at 37°C. The cell density of Staphylococcus aureus cultures after an overnight period was increased to 600 ns in BHI broth. The optical density at m (OD600) was adjusted to 1, and then 10 times in PBS buffer. Dilute to -2 dilution. Spread 200 microliters of cell suspension onto a BHI agar plate. The plates containing Staphylococcus aureus were dried in sterile air for approximately 10-20 minutes. I left it there. I placed three copies of 20 μL of isolated LAB on the Staphylococcus aureus flora in a spotted pattern. The plate was left to dry, and then incubated aerobically at 37°C overnight. The plate was photographed, and the obstructed area was measured in millimeters as the purified area around the spot. Determined. Growth inhibition is determined when the bacterial strain develops grapes in the spot area indicated as (+) in Table 2. It is observed that cocci strains can be overgrown. Staphylococcus strains develop a spotted pattern. If the bacterial strain is able to grow more than the one that became the growth inhibitor, the growth inhibition shown as (-) in Table 2 is considered to be Not detected.

[0152] Five LAB strains showed significant growth inhibitory effects against Staphylococcus aureus, and also, spot It was identified as having an inhibitory region exceeding 1 mm around the rhizome. Lactobacillus lam Nosus LGG (Chr. Hansen) was used as a control commercially available probiotic strain. It was used. Lactobacillus rhamnosus inhibited the growth of all of the Staphylococcus test strains. It is not possible to do so, and Lactobacillus rhamnosus LGG does not provide any purification area. I couldn't do it.

[0153] [Table 2]

[0154] Significant inhibition of CC1 was determined, and this clonal complex type of Staphylococcus aureus is particularly atopic. - It is associated with Staphylococcus aureus infection in genital dermatitis (Clausen et al.). (2017)Br.J.Dermatol.177:1394-1400.Doi 10 (.1111 / bjd.15470).

[0155] Lactobacillus acidophilus NCFM, Lactobacillus salivarius Ls-3 3. Bifidobacterium lactis 420, Lactobacillus acidophilus La- 14 and Propionibacterium yensenii P63 (all commercially available from DuPont) All of these are related to tight bonding function by improving the skin's barrier function. It is related to conditions that can be improved, such as atopic dermatitis. However, in a spot-on loan trial using CC1, these commercially available probiotics None of the Tix strains were able to inhibit the growth of CC1, and therefore Staphylococcus It cannot prevent or treat bacterial infections.

[0156]

number

[0157]

number

[0158]

number

[0159]

number

[0160]

number

[0161]

number

Claims

1. A bacterial strain selected from Lactobacillus plantarum, wherein the Lactobacillus plantarum is Lactobacillus plantarum LB244R deposited as DSM32996.

2. The bacterial strain according to claim 1, wherein the bacterial strain is an isolated bacterial strain.

3. A composition comprising one or more bacterial strains as described in claim 1 or 2.

4. The composition according to claim 3, wherein one or more of the bacterial strains are provided as one or more viable strains, one or more dead or inactivated strains, one or more strain lysates, one or more strain metabolites, or a combination thereof.

5. The composition according to claim 3 or 4, wherein the composition is an emulsion, oil, gum, paste, powder, talc, lotion, custard, foam, cream, gel, ointment, suspension, mist, or liquid.

6. The composition according to any one of claims 3 to 5, wherein the composition is a topical composition, an oral composition, or a rectal composition.

7. The concentration of the aforementioned bacterial strain is 10 ３ ~10 １４ A composition according to any one of claims 3 to 6, which is within the range of colony-forming units (CFUs).

8. The composition according to any one of claims 3 to 7, wherein the bacterial strain described in claim 1 or 2 is the only bacterium present in the composition.

9. A composition according to any one of claims 3 to 8, for use in treating, mitigating, inhibiting, preventing, and / or inhibiting the growth of pathogenic microorganisms.

10. A composition according to any one of claims 3 to 9, for use in treating, mitigating, suppressing, and / or preventing infections of one or more pathogenic bacteria in mammals.

11. A composition according to any one of claims 3 to 10 for use in treating, mitigating, suppressing, and / or preventing infections of one or more antibiotic-resistant bacteria in mammals.

12. The composition according to any one of claims 10 or 11, wherein the bacterial infection is a staphylococcal infection in a mammal.

13. A composition according to any one of claims 10 to 12 for use in treating, mitigating, suppressing, and / or preventing diseases resulting from staphylococcal infections.

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