Lactobacillus muci genosus BLF03 and application thereof in resisting drug-resistant staphylococcus aureus

Abstract

The application belongs to the technical field of microorganisms, and specifically discloses a fermented Lactobacillus muciapparius BLF03 and application thereof in resisting drug-resistant Staphylococcus aureus. The drug-resistant Staphylococcus aureus is Staphylococcus aureus resistant to drugs targeting beta-lactamase. The fermented Lactobacillus muciapparius BLF03 has been preserved in the China General Microbiological Culture Collection Center on November 6, 2025, and the preservation number is CGMCC No. 36521. The application provides the fermented Lactobacillus muciapparius BLF03 for resisting Staphylococcus aureus resistant to drugs targeting beta-lactamase, which can well relieve infection symptoms induced by drug-resistant Staphylococcus aureus, reduce the expression level of procalcitonin in the body after infection, and improve inflammatory stress response caused by infection, thereby providing a new safe and efficient strain selection for products resisting drug-resistant Staphylococcus aureus.

Description

Technical Field

[0001] This application belongs to the field of microbial technology, specifically relating to a fermenting Lactobacillus mucinus BLF03 and its application in drug-resistant Staphylococcus aureus. Background Technology

[0002] Staphylococcus aureus is a common pathogen widely found in the human environment. It can be transmitted through respiratory droplets, skin and mucous membrane contact, and other routes, causing various diseases such as skin and soft tissue infections, pneumonia, and sepsis, posing a significant threat, especially to immunocompromised individuals and postoperative patients. Antibiotics (such as methicillin, tetracycline, ciprofloxacin, clindamycin, erythromycin, oxacillin, penicillin G, amoxicillin / clavulanic acid, or ampicillin) are commonly used techniques to target this pathogen, and they greatly improved the situation when they were first introduced. However, with the widespread use of clinical antibiotics, Staphylococcus aureus has gradually mutated and developed drug resistance, and its resistance spectrum continues to expand, leading to limited clinical treatment options and persistently high infection recurrence and mortality rates.

[0003] Furthermore, infection with drug-resistant Staphylococcus aureus can activate an excessive inflammatory response in the body, leading to abnormally elevated levels of inflammatory markers such as procalcitonin (PCT), exacerbating tissue damage and further increasing the difficulty of treatment. Current core treatment methods still rely on a few potent antibiotics such as vancomycin and linezolid, but long-term use can easily induce further evolution of drug resistance and has side effects such as nephrotoxicity and bone marrow suppression.

[0004] Probiotics have garnered significant attention in the field of anti-infection due to their unique advantages, including safety, non-toxicity, low likelihood of inducing drug resistance, and ability to regulate host microecological balance. However, existing Lactobacillus strains primarily focus on antifungal or common bacterial infections, with a scarcity of specific inhibitory strains against drug-resistant Staphylococcus aureus. Furthermore, some strains exhibit weak inhibitory activity and insufficient colonization capacity, failing to meet clinical needs. Therefore, developing a novel probiotic strain with strong inhibitory activity against drug-resistant Staphylococcus aureus, high biosafety, and the ability to simultaneously regulate infection-induced inflammatory responses is of significant practical importance and application value for enriching anti-infection methods, reducing antibiotic dependence, and improving clinical treatment outcomes. Summary of the Invention

[0005] The purpose of this application is to at least solve at least one technical problem existing in the prior art. Based on this, this application provides a *Lactobacillus fermentans* BLF03, which is classified as *Lactobacillus fermentans*. Limosilactobacillus fermentumThe above-mentioned *Lactobacillus mucinus* BLF03 was deposited on November 6, 2025, at the China General Microbiological Culture Collection Center (CGMCC), located at No. 3, Courtyard 1, Beichen West Road, Chaoyang District, Beijing, with accession number CGMCC No. 36521. The applicant discovered that the aforementioned *Lactobacillus mucinus* BLF03 can be used in the preparation of products resistant to drug-resistant *Staphylococcus aureus*, which are *Staphylococcus aureus* strains resistant to drugs targeting β-lactamases.

[0006] Among them, the above-mentioned drugs may be methicillin, tetracycline, ciprofloxacin, clindamycin, erythromycin, oxacillin, penicillin G, amoxicillin / clavulanic acid, or ampicillin.

[0007] Based on this, this application also provides a pharmaceutical composition for combating drug-resistant Staphylococcus aureus, wherein the drug-resistant Staphylococcus aureus is a Staphylococcus aureus resistant to drugs targeting β-lactamases; the active ingredient of the pharmaceutical composition includes the aforementioned *Lactobacillus fermentum* BLF03. The pharmaceutical composition can alleviate infections induced by drug-resistant Staphylococcus aureus resistant to β-lactamases.

[0008] Among them, the fermented Lactobacillus mucinus BLF03 was a bacterial suspension; its concentration was 10. 4 CFU / mL-10 8 CFU / mL.

[0009] Furthermore, the above-mentioned pharmaceutical composition also includes pharmaceutically acceptable excipients.

[0010] Furthermore, this application also found that the aforementioned fermenting Lactobacillus mucinus BLF03 can be used in the preparation of products that reduce procalcitonin expression levels. By reducing procalcitonin expression levels, the inflammatory response is further alleviated.

[0011] Finally, this application also found that the above-mentioned fermented Lactobacillus mucinus BLF03 can be used in the preparation of products resistant to Candida albicans and / or Candida krusei.

[0012] The beneficial effects of this application are as follows: This application proposes a fermentation strain of *Lactobacillus mucosae* BLF03 that targets drugs resistant to β-lactamases. It can effectively alleviate infection symptoms induced by drug-resistant *Staphylococcus aureus*, reduce the expression level of the inflammatory marker procalcitonin (PCT) in the body after infection, improve the inflammatory stress response induced by infection, and protect against tissue damage caused by its invasion. At the same time, it has excellent biocompatibility and colonization ability, can enhance the defense against drug-resistant *Staphylococcus aureus*, and has targeted prevention and adjuvant treatment effects against drug-resistant *Staphylococcus aureus* infection, providing a new safe and efficient strain selection for anti-drug-resistant *Staphylococcus aureus* products. Attached Figure Description

[0013] Figure 1 The colony morphology of fermenting Lactobacillus mucinus BLF03 is shown on MRS solid medium (A) and blood agar plate (B), respectively. Figure 2 The image shown is a Gram staining image of fermenting Lactobacillus mucinus BLF03; Figure 3 The image shows the results of a hemolysis experiment using fermented Lactobacillus mucinus BLF03. Figure 4 The image shows the drug susceptibility test results for Lactobacillus fermentans BLF03. Figure 5 The figure shown is a growth curve of fermented Lactobacillus mucinus BLF03; Figure 6 The figure shown is a graph of lactic acid production from fermentation of Lactobacillus mucilaginosus BLF03. Figure 7 The figure shows the cumulative hatching rate curves of zebrafish embryos treated with different concentrations of Lactobacillus fermentum BLF03. Figure 8 The image shows the acid resistance test results of fermenting Lactobacillus mucilaginosus BLF03; Figure 9 The figure shown is a graph of the high-temperature resistance test results of fermenting Lactobacillus mucilaginosus BLF03; Figure 10 The image shows the results of treating drug-resistant Staphylococcus aureus with different concentrations of Lactobacillus fermentum BLF03 (A, B, and C correspond to the control group, 10, and 10, respectively). 7 CFU / mL, 10 4 (CFU / mL) Figure 11 The image shows the results of cross-inoculation of fermenting Lactobacillus mucinus BLF03 and drug-resistant Staphylococcus aureus. Figure 12 The figure shown is a comparison of PCT expression levels in a model of Staphylococcus aureus infection treated with fermented Lactobacillus mucin BLF03. Figure 13 The image shows the mycelial transformation results of *Candida albicans* treated with different concentrations of *Lactobacillus fermentum* BLF03 (AD corresponds to Control, 10, and 20%). 6 CFU / mL, 10 7 CFU / mL, 10 8 (CFU / mL concentration experimental group) Figure 14The image shown is one of the results of the co-culture experiment of *Lactobacillus fermentum* BLF03, *Pediococcus lactis* BPA03, *Lactobacillus plantarum* BLP03, and *Lactobacillus rhamnosus* BLR03 with *Candida albicans* (AE corresponds to the control group, the experimental groups of *Lactobacillus fermentum* BLF03, *Pediococcus lactis* BPA03, *Lactobacillus plantarum* BLP03, and *Lactobacillus rhamnosus* BLR03, respectively). Figure 15 The second figure shows the results of the co-culture experiment of Lactobacillus fermentum BLF03, Pediococcus lactis BPA03, Lactobacillus plantarum BLP03, and Lactobacillus rhamnosus BLR03 with Candida albicans. Figure 16 The image shown is one of the results of a co-culture experiment between different concentrations of *Lactobacillus fermentum* BLF03 and *Candida albicans* (AG corresponds to the control group and 10...). 4 CFU / mL, 10 5 CFU / mL, 10 6 CFU / mL, 10 7 CFU / mL, 10 8 CFU / mL, 10 9 (Experimental group with CFU / mL) Figure 17 The second figure shows the results of the co-culture experiment of different concentrations of fermenting Lactobacillus mucin BLF03 and Candida albicans. Figure 18 The figure shown is a comparison of PCT expression levels in a Candida albicans infection model treated with fermented Lactobacillus mucin BLF03. Figure 19 The image shows the results of cross-inoculation of Lactobacillus fermentum BLF03 and Candida albicans. Figure 20 The results of the antibacterial test of Lactobacillus fermentum BLF03 against Candida krusei and Candida tropicalis are shown (A and B are the control groups for Candida krusei and Candida tropicalis, respectively, and C and D are the Lactobacillus fermentum BLF03 treatment groups for Candida krusei and Candida tropicalis, respectively). Detailed Implementation

[0014] The following will provide a clear and complete description of the concept and technical effects of this application in conjunction with the embodiments and accompanying drawings, so as to fully understand the purpose, solution and effects of this application. It should be noted that, unless otherwise specified, the embodiments and features in the embodiments of this application can be combined with each other.

[0015] Example 1 1. Morphology of the strain Lactobacillus fermentum BLF03 was inoculated onto blood agar plates and MRS solid medium, respectively. It grew well under conditions of 37 ℃ and 5% CO2. The colony morphology showed that the colonies were mostly light yellow or milky white, with a relatively uniform color, and no obvious pigment production. Figure 1 AB). Gram staining results showed: short rods, arranged singly, in pairs, or in short chains, with Gram-positive staining. Figure 2 ).

[0016] 2. Physiological and biochemical identification of the strain Colonies of *Lactobacillus fermentum* BLF03 were selected and prepared into a bacterial suspension for biochemical reaction testing. The results of the biochemical reaction are shown in Table 1.

[0017] Table 1 It is evident that the fermenting *Lactobacillus mucinus* strain BLF03 can utilize multiple carbon sources such as glucose (A_GLPRB+), lactose (A_LALT+), and melibiose (C_DGUA+), but is negative for arabinose (A_ARARR-) and maltose (A_LISO-). It can break down amino acids such as leucine (A_LLEUH+) and proline (A_LPROB+), but is negative for histidine (A_LHIST-), phenylalanine (A_LPHET-), and tryptophan (A_LTRY-). Other biochemical reactions: nitrate reduction test (N_ALALH-) and urease test (S_URE-) were negative; β-glucosidase (M_BDGLU-), phosphatase (M_PHOS-), and N-acetylglucosaminease (M_NAG-) activities were absent, but β-galactosidase (M_BDGAL+) activity was positive.

[0018] 3. Hemolysis test of the strain Colonies of *Lactobacillus fermentata* (BLF03) were picked using an inoculation loop and inoculated onto blood agar plates. *Escherichia coli* ATCC25922 was used as a negative control, and *Staphylococcus aureus* ATCC29213 as a positive control. The plates were incubated at 35 °C and 5% CO2 for 48 h. The presence or absence of hemolytic rings was observed on the blood agar plates. The test results are as follows: Figure 3 As shown, the negative control Escherichia coli ATCC25922 did not show a hemolytic zone on blood agar plates, while the positive control Staphylococcus aureus ATCC29213 showed a hemolytic zone on blood agar plates. No hemolytic zone was formed around Lactobacillus fermentatus BLF03, which was determined to be a non-hemolytic strain (γ-hemolysis), suggesting that it may have low cytotoxicity when colonizing the host.

[0019] 4. Drug susceptibility testing of strains The susceptibility of *Lactobacillus fermentata* BLF03 to antimicrobial agents was determined using the disk diffusion method. *Lactobacillus fermentata* BLF03 was spread and inoculated onto the surface of MRS medium. Disks containing penicillin, ampicillin, imipenem, erythromycin, and clindamycin were placed on the medium surface using tweezers. The medium was then incubated at 35 °C in a 5% CO2 incubator, and the diffusion values ​​were measured. The test results are shown below. Figure 4 As shown in Table 2.

[0020] Table 2 It is evident that Lactobacillus fermentans BLF03 is sensitive to most antibacterial drugs, including glycopeptides, β-lactams, and macrolides.

[0021] 5. Determination of the growth and acid production characteristics of the strain The growth curve of *Lactobacillus myxobolus* BLF03 cultured in an aerobic flask containing adult blood culture at 37°C is shown below. Figure 5 As shown, the lag phase is about 2 hours, the logarithmic growth phase is 4-12 hours, and it enters the stationary phase after 24 hours, with the maximum R value reaching about 3950.

[0022] Lactobacillus fermentum BLF03 was inoculated into MRS liquid medium and cultured in a shaker at 35 ℃ for 14 h. The strain concentration was then adjusted to 1×10⁻⁶. 6 The lactic acid concentration was measured at CFU / mL and then inoculated into fresh MRS liquid medium. The inoculation was done at a volume fraction of 5% in 50 mL centrifuge tubes and incubated in a 37 ℃, 150 r / min shaker. The lactic acid concentration in the fermentation supernatant was then measured using a Hitachi fully automated biochemical analyzer. The acidity of the fermentation broth for *Lactobacillus mucilaginosus* BLF03 was as follows: Figure 6 As shown, the lactic acid production in the fermentation broth increased with the culture time, reaching a concentration of 21.42 mM at 8 h, and the pH value decreased from the initial 6.5 to 3.8, demonstrating a strong acid production capacity.

[0023] 6. Safety evaluation of the strain Different concentrations of fermented Lactobacillus mucilaginosus BLF03 bacterial suspension (10 5 -10 8 Zebrafish embryos were treated with CFU / mL (all bacterial cultures were prepared in E3 medium). One hundred healthy zebrafish embryos (3 pdh, normally reproduced, and without deformities) were placed in the following five experimental groups: control, 10... 5 CFU / ml, 10 6 CFU / ml, 10 7 CFU / ml, 10 8CFU / ml, incubated for 96 h and observed under culture conditions of 26±1 ℃, then immediately calculated the exposure time at 24, 48, 72, and 96 h. The solution was changed every 24 hours to ensure the stability of all parameters. During exposure, embryonic morphological changes were observed at 24, 48, 72, and 96 hours, with embryonic cell damage, yolk coagulation, embryonic turbidity, and absence of heartbeat being signs of death. Cumulative hatchability was calculated as follows: Figure 7 As shown, the embryo survival rate in each concentration group was >95%, and no toxic phenotypes such as malformation or pericardial edema were observed. The LD50 was >10. 8 The CFU / mL level indicates that fermented Lactobacillus mucinus BLF03 has no significant acute toxicity to zebrafish embryos.

[0024] 7. Acid resistance test of the strain 200 μL of purified *Lactobacillus fermentum* BLF03 suspension was inoculated into 10 mL of MRS broth at pH 3.0, 3.5, and 7.5, respectively, and cultured statically at 37 ℃ to the logarithmic growth phase. Samples were taken at 0, 2, 4, and 6 h. 100 μL of the cultured *Lactobacillus fermentum* BLF03 suspension was evenly spread onto MRS solid medium and cultured at 37 ℃. Viable cell counts were performed after 24 h, and the results are shown below. Figure 8 As shown.

[0025] 8. High-temperature resistance test of the strain 200 μL of purified *Lactobacillus fermentum* BLF03 suspension was inoculated into 10 mL of MRS broth at temperatures of 40℃, 50℃, and 60℃, respectively. The cultures were incubated statically at 37℃ until the logarithmic growth phase. Samples were taken at 0, 30, 60, and 90 min. 100 μL of the incubated *Lactobacillus fermentum* BLF03 suspension was evenly spread onto MRS solid medium and incubated at 37℃. Viable cell counts were performed after 24 h, and the results are shown below. Figure 9 As shown.

[0026] 9. Effects of strains on drug-resistant Staphylococcus aureus Staphylococcus aureus was obtained from blood cultures of clinical patients. Clinical drug susceptibility testing of the bacterium was performed using the MIC method. The results are shown in Table 3 (S represents sensitive, R represents resistant). The bacterium is resistant to multiple antibiotics and was positive in the methicillin resistance test.

[0027] Table 3 Co-culture experiments were conducted with different concentrations of bacterial strains and drug-resistant Staphylococcus aureus: Experimental design: The experimental strain of *Lactobacillus fermentatus* BLF03 was inoculated into MRS liquid medium for second-generation activation. After 8 h of activation, the strain was inoculated again. 50 μL of drug-resistant *Staphylococcus aureus* culture was inoculated into liquid medium No. 13 (50 mL) and cultured in a shaker at 37 ℃ for 16 h for activation.

[0028] Experimental groups: control group: 10 6 CFU / mL drug-resistant Staphylococcus aureus; Experimental group: 10 6 CFU / mL drug-resistant Staphylococcus aureus was compared with a concentration of 10 4 CFU / mL, 10 7 CFU / mL *Lactobacillus fermentum* BLF03 was co-inoculated into 15 mL centrifuge tubes containing 10 mL of MRS medium and incubated at 37 °C for 48 h. After incubation, the culture was transferred to blood agar plates, and viable counts were performed on all strains in each group. The experimental groups included a control group and 10... 7 CFU / mL, 10 4 CFU / mL, test results are as follows Figure 10 (In the figure, A, B, and C correspond to the control group and 10, respectively) 7 CFU / mL, 10 4 As shown in the CFU / mL figure, *Lactobacillus fermentum* BLF03 has an inhibitory effect on drug-resistant *Staphylococcus aureus*, and the effect is further observed when the bacterial concentration of *Lactobacillus fermentum* BLF03 is 10... 7 Drug-resistant Staphylococcus aureus was completely inhibited at CFU / mL.

[0029] The fermenting Lactobacillus mucinus BLF03 and the drug-resistant Staphylococcus aureus were cross-inoculated onto a blood agar platform, and the test results are as follows. Figure 11 As shown, Staphylococcus aureus is significantly inhibited at the intersection of the two, and Lactobacillus fermentum BLF03 and methicillin-resistant Staphylococcus aureus have an antagonistic effect.

[0030] 10. Strains alleviate Staphylococcus aureus infections A Staphylococcus aureus infection model (using the aforementioned drug-resistant Staphylococcus aureus) was established using zebrafish larvae. Experimental groups were as follows: Control group: normal zebrafish larvae, without infection treatment, cultured only in fish tank water; Model group: infected with Staphylococcus aureus only, without the addition of *Lactobacillus fermentum* BLF03; BLF03 group: *Lactobacillus fermentum* BLF03 was added first, followed by infection with Staphylococcus aureus. PCT expression levels were detected in different groups, and the results are shown below. Figure 12 As shown, fermented Lactobacillus mucinus BLF03 significantly improved the PCT elevation induced by Staphylococcus aureus infection in zebrafish larvae.

[0031] 11. Effects of strains on the transformation of Candida albicans into hyphae With a density of 10 6 CFU / mL Candida albicans cells were placed in a culture medium and treated with different concentrations of Lactobacillus fermentum BLF03 at 37 ℃ for 4 hours. Figure 4 The AD experimental group was divided into Control and 10 6 CFU / mL, 10 7 CFU / mL, 10 8 (CFU / mL), followed by imaging of the fungal hyphae using an inverted microscope (Cai Kang Optical Microscope, China). The results are as follows: Figure 13 As shown in AD, it can be observed that as the concentration of fermenting Lactobacillus mucin BLF03 increases, Candida albicans mycelium is significantly inhibited.

[0032] 12. Co-culture test of different lactobacilli and Candida albicans Lactobacillus fermentum BLF03, Pediococcus lactis BPA03, Lactobacillus plantarum BLP03, and Lactobacillus rhamnosus BLR03 were inoculated into MRS liquid medium for two generations of activation. After 8 h of activation, the culture was inoculated. 50 μL of Candida albicans culture was inoculated into 50 mL of liquid medium (C13) and cultured at 37 °C for 16 h on a shaker. The viable cell counts of Lactobacillus fermentum BLF03, Pediococcus lactis BPA03, Lactobacillus plantarum BLP03, and Lactobacillus rhamnosus BLR03 after activation were all controlled to be 1 × 10⁻⁶. 9 CFU / mL, the viable count of activated Candida albicans was 1×10⁻⁶. 8 CFU / mL. Experimental design: 200 μL of *Lactobacillus fermentum* BLF03, *Pediococcus lactis* BPA03, *Lactobacillus plantarum* BLP03, and *Lactobacillus rhamnosus* BLR03 bacterial suspensions were simultaneously inoculated with 200 μL of *Candida albicans* bacterial suspensions into 10 mL (15 mL centrifuge tube volume) of MRS liquid medium. The control group consisted of 200 μL of *Candida albicans* bacterial suspension inoculated into 10 mL of MRS liquid medium. The cultures were incubated at 37 ℃ for 48 h. Viable counts of *Candida albicans* in each group were performed using Sabouraud SDA (fungal selective plate) solid medium. The results are as follows: Figure 14 and Figure 15 As shown, Figure 14 The middle and lower halves of the spectrum were the control group, Lactobacillus fermentum BLF03, Pediococcus lactis BPA03, Lactobacillus plantarum BLP03, and Lactobacillus rhamnosus BLR03, respectively. It can be seen that compared with other lactobacilli, Lactobacillus fermentum BLF03 has a significant inhibitory effect on Candida albicans.

[0033] 13. Co-culture experiment of different strain concentrations with Candida albicans The *Lactobacillus fermentans* BLF03 to be tested was inoculated into MRS liquid medium for second-generation activation. After 8 h of second-generation activation, the bacteria were inoculated again. 50 μL of *Candida albicans* culture was inoculated into liquid medium No. 13 (50 mL) and cultured in a shaker at 37 ℃ for 16 h for activation.

[0034] Experimental groups: control group: 10 6 CFU / mL Candida albicans; Experimental group: 10 6 CFU / mL Candida albicans was compared with a concentration of 10 4 CFU / mL, 10 5 CFU / mL, 10 6 CFU / mL, 10 7 CFU / mL, 10 8 CFU / mL, 10 9 CFU / mL, 10 10 CFU / mL *Lactobacillus fermentata* BLF03 was co-inoculated into 15 mL centrifuge tubes containing 10 mL of MRS medium and incubated at 37 ℃ for 48 h. Viable counts of *Candida albicans* in each group were performed using Sabouraud SDA (fungal selective plate) solid medium. The results are shown below. Figure 16 and Figure 17 As shown, Figure 16 In the middle, AG represents the control group and 10. 4 CFU / mL, 10 5 CFU / mL, 10 6 CFU / mL, 10 7 CFU / mL, 10 8 CFU / mL, 10 9 CFU / mL.

[0035] 14. Strains alleviate fungal infections A Candida albicans infection model was established using zebrafish larvae. Experimental groups were as follows: Control group: normal zebrafish larvae, without infection treatment, cultured only in fish tank water; Model-Candida albicans group: infected only with Candida albicans, without the addition of Lactobacillus; 5-F group: positive control (5-fluorocytosine, an antifungal drug), administered before infection; BLF03 group: first treated with Lactobacillus fermentum BLF03, then infected with Candida albicans. PCT expression levels were measured in different groups, and the results are shown below. Figure 18 As shown, fermented Lactobacillus mucinus BLF03 significantly improved the PCT elevation induced by Candida albicans infection in zebrafish larvae.

[0036] 15. Antibacterial experiment between strain and Candida albicans Lactobacillus fermentum BLF03 and Candida albicans were cross-inoculated onto a blood agar platform, and the test results are as follows: Figure 19 As shown, Candida albicans is significantly inhibited at the intersection of the two, and Lactobacillus fermentum BLF03 has an antagonistic effect on Candida albicans.

[0037] 16. Antimicrobial test of strains against Candida krusei and Candida tropicalis The *Lactobacillus fermentata* BLF03 to be tested was inoculated into MRS liquid medium for second-generation activation. After 8 h of second-generation activation, the bacteria were inoculated again. 50 μL of *Candida krusei* and *Candida tropicalis* bacterial suspensions were inoculated into liquid medium No. 13 (50 mL) and cultured in a shaker at 37 ℃ for 16 h for activation.

[0038] The viable count of activated Lactobacillus mucinus BLF03 was controlled to be 1×10⁻⁶. 9 CFU / mL, the viable count of activated Candida krusei and Candida tropicalis was 1×10⁻⁶. 8 CFU / mL. Experimental design: 200 μL of *Lactobacillus fermentatus* BLF03 culture was inoculated into 10 mL (15 mL centrifuge tube volume) of MRS liquid medium, along with 200 μL of *Candida krusei* and *Candida tropicalis* culture, respectively. The control group consisted of 200 μL of *Candida krusei* and 200 μL of *Candida tropicalis* culture inoculated into 10 mL of MRS liquid medium. The cultures were incubated at 37 ℃ for 48 h. Viable counts of *Candida albicans* in each group were performed using Sabouraud SDA (fungal selective plate) solid medium. The results are shown below. Figure 20 As shown in the figure (A and B are the control groups for Candida krusei and Candida tropicalis, respectively, and C and D are the treatment groups for Candida krusei and Candida tropicalis with Lactobacillus fermentum BLF03, respectively), the results show that Lactobacillus fermentum BLF03 can inhibit the growth of Candida krusei, but the inhibitory effect on Candida tropicalis is not obvious.

[0039] The above description is merely a preferred embodiment of this application. This application is not limited to the above-described embodiments. Any embodiment that achieves the technical effect of this application using the same means should fall within the protection scope of this application. Within the protection scope of this application, the technical solutions and / or implementation methods can have various modifications and variations.

Claims

1. A fermenting Lactobacillus mucinus BLF03, characterized in that, The fermenting *Lactobacillus fermentatus* BLF03 is classified as *Lactobacillus fermentatus*. Limosilactobacillus fermentum It was deposited on November 6, 2025, at the China General Microbiological Culture Collection Center (CGMCC), located at No. 3, Courtyard 1, Beichen West Road, Chaoyang District, Beijing, with accession number CGMCC No. 36521.

2. The application of the fermented Lactobacillus mucinus BLF03 according to claim 1 in the preparation of products resistant to drug-resistant Staphylococcus aureus, characterized in that, The drug-resistant Staphylococcus aureus is a Staphylococcus aureus that is resistant to drugs that target β-lactamases.

3. The application according to claim 2, characterized in that, The drugs mentioned are methicillin, tetracycline, ciprofloxacin, clindamycin, erythromycin, oxacillin, penicillin G, amoxicillin / clavulanic acid, or ampicillin.

4. A pharmaceutical composition for combating drug-resistant Staphylococcus aureus, characterized in that, The drug-resistant Staphylococcus aureus is a Staphylococcus aureus that is resistant to drugs targeting β-lactamase; the active ingredient of the pharmaceutical composition includes Lactobacillus fermentans BLF03 as described in claim 1.

5. The pharmaceutical composition according to claim 4, characterized in that, The drugs mentioned are methicillin, tetracycline, ciprofloxacin, clindamycin, erythromycin, oxacillin, penicillin G, amoxicillin / clavulanic acid, or ampicillin.

6. The pharmaceutical composition according to claim 4, characterized in that, The fermented Lactobacillus mucinus BLF03 is a bacterial suspension.

7. The pharmaceutical composition according to claim 6, characterized in that, The concentration of the fermented Lactobacillus mucinus BLF03 was 10. 4 CFU / mL-10 8 CFU / mL.

8. The pharmaceutical composition according to any one of claims 4 to 7, characterized in that, It also includes pharmaceutically acceptable excipients.

9. The use of the fermented Lactobacillus mucinus BLF03 according to claim 1 in the preparation of products with reduced procalcitonin expression levels.

10. A pharmaceutical composition for reducing procalcitonin expression levels, characterized in that, The active ingredient of the pharmaceutical composition includes the fermenting Lactobacillus mucinus BLF03 as described in claim 1.

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