Staphylococcus aureus is currently a significant multidrug-resistant bacterium, causing severe healthcare-associated and community-acquired infections worldwide. The current antibiotic regimen against this pathogen is becoming ineffective due to resistance, in addition, they disrupt the normal microbiota. It highlights the urgent need for a pathogen-specific drug with high antibacterial efficacy against S. aureus. α-Viniferin, a bioactive phytochemical compound, has been reported to have excellent anti-Staphylococcus efficacy as a topical agent. However, so far, there were no clinical trials that have been conducted to elucidate its efficacy. The present study aimed to investigate the antibacterial efficacy of α-viniferin against S. aureus in a ten-day clinical trial. Based on the results, α-viniferin showed 50% minimum inhibitory concentrations (MIC50 values) of 7.8 μg/ml in culture broth medium. α-Viniferin was administered in the nares three times a day for ten days using a sterile cotton swab stick. Nasal swab specimens were collected before (0 days) and after finishing the trial (10th day), and then analyzed. In the culture and RT-PCR-based analysis, S. ureus was reduced significantly: 0.01. In addition, 16S ribosomal RNA-based amplicon sequencing analysis showed that S. aureus reduced from 51.03% to 23.99% at the genus level. RNA-seq analysis was also done to gain insights into molecular mechanisms of α-viniferin against S. aureus, which revealed that some gene groups were reduced in 5-fold FC cutoff at two times MIC conditions. The study results demonstrate α-viniferin as a potential S. aureus-specific drug candidate.

Mycobacterium tuberculosis (M. tb), the etiological agent of tuberculosis (TB), poses a severe challenge for public health and remains the number one cause of death as a single infectious agent. There are 10 million active cases of TB per year with 1.5 million deaths, and 2–3 billion people are estimated to harbor latent M. tb infection. Moreover, the emergence of multi-drug-resistant (MDR), extremely-drug-resistant (XDR), and the recent totally drug-resistant (TDR) M. tb is becoming a global issue that has fueled the need to find new drugs different from existing regimens. In these circumstances, probiotics can be a potential choice, so we focused on developing them as an anti-tuberculosis drug candidate. Here, we report the anti-tubercular activities of Lacticaseibacillus rhamnosus PMC203 isolated from the vaginal microbiota of healthy women. PMC203 exhibited a promising intracellular killing effect against both drug-sensitive and resistant M. tb infected murine macrophage cell line RAW 264.7 without showing any cytotoxicity. Additionally, it also inhibited the growth of M. tb under broth culture medium. PMC203 did not cause weight change or specific clinical symptoms in a 2-week repeated oral administration toxicity test in a guinea pig model. Here, we also found that PMC203 induces autophagy in a dose dependent manner by increasing the signal of well-known autophagy gene markers, suggesting a possible intracellular killing mechanism.

pathogens, modifying intestinal immune responses, and reducing the risk of infection [12][13][14][15]. Lactobacillus fermentum is one of the dominant Lactobacilli in a healthy woman's vaginal tract and intestine [16,17]. Previous studies have defined L. fermentum as a possible probiotic candidate for protecting the intestine against pathogens and regulating microfloral balance [18,19]. L. fermentum can inhibit intestinal pathogen growth by producing inhibitory compounds including H 2 O 2 , bacteriocin, and biosurfactants and improve intestinal bacteria flora by reducing Clostridium perfringens [20][21][22]. Moreover, other studies have reported that L. fermentum shows probiotic potential against gram-negative bacteria, including E. coli, Salmonella Typhimurium, and Klebsiella pneumoniae biofilm [23,24].CRE are gram-negative bacteria that seriously threaten public health, and infections due to these organisms are associated with significant morbidity and mortality [25]. Carbapenemase (including new Delhi metallo-β-Carbapenem-resistant Enterobacteriaceae (CRE) that produce Klebsiella pneumoniae carbapenemase are increasingly reported worldwide and have become more and more resistant to nearly all antibiotics during the past decade. The emergence of K. pneumoniae strains with decreased susceptibility to carbapenems, which are used as a last resort treatment option, is a significant threat to hospitalized patients worldwide as K. pneumoniae infection is responsible for a high mortality rate in the elderly and immunodeficient individuals. This study used Lactobacillus fermentum as a candidate probiotic for treating CRE-related infections and investigated its effectiveness. We treated mice with L. fermentum originating from the vaginal fluid of a healthy Korean woman and evaluated the Lactobacilli's efficacy in preventive, treatment, nonestablishment, and colonization mouse model experiments. Compared to the control, pre-treatment with L. fermentum significantly reduced body weight loss in the mouse models, and all mice survived until the end of the study. The oral administration of L. fermentum after carbapenemresistant Klebsiella (CRK) infection decreased mortality and illness severity during a 2-week observation period and showed that it affects other strains of CRK bacteria. Also, the number of Klebsiella bacteria was decreased to below 5.5 log 10 CFU/ml following oral administration of L. fermentum in the colonization model. These findings demonstrate L. fermentum's antibacterial activity and its potential to treat CRE infection in the future.

Human vaginal microorganisms play an important role in maintaining good health throughout the human life cycle. An imbalance in the vaginal microbiota is associated with an increased risk of pelvic inflammatory disease (PID). This study aimed to characterize and compare vaginal microbial profiles of premenopausal Korean women with and without PID. 74 Korean premenopausal female vaginal samples were obtained; 33 were from healthy women (a control group) and 41 from PID patients. Vaginal fluid samples were collected from the vaginal wall and posterior cervix and then analyzed by 16S ribosomal ribonucleic acid (rRNA) gene-based amplicon sequencing. Results showed a significant difference between the vaginal microbial communities of the two groups (Jensen-Shannon, p = 0.014; Bray-Curtis, p = 0.009; Generalized UniFrac, p = 0.007; UniFrac, p = 0.008). Lactobacillus accounted for the highest percentage (61.0%) of the control group but was significantly decreased (34.9%) in PID patients; this was the most significant difference among all bacterial communities (p = 0.028, LDA effect size = 5.129). In addition, in the PID patient group, species diversity significantly increased (Simpson, p = 0.07) as the proportion of various pathogens increased evenly, resulting in a polymicrobial infection. Similarly, lactate, which constituted the highest percentage of the organic acids in the control group, was significantly decreased in the PID patient group (p = 0.04). The present study’s findings will help understand PID from the microbiome perspective and are expected to contribute to the development of more efficient PID diagnosis and treatment modalities.

Outbreaks of carbapenem-resistant Enterobacteriaceae (CRE), especially Klebsiella pneumoniae (CRKP), are commonly reported as severe infections in hospitals and long-term care settings, and their occurrence is increasing globally. Conventional antibiotics used for treating CRE have become ineffective due to resistance development. Furthermore, their safety issues restrict their availability and use for CRE treatment. Therefore, developing new drugs different from existing drugs to combat this deadly menace is urgently needed. Probiotics can be a potential option in this context, as probiotics’ efficacy against a variety of infectious illnesses has already been well established. Here, we report the effect of the Bacillus velezensis strain isolated from Gochang Bokbunja vinegar in Korea on CRE infection using two mouse models. Data showed that pretreatment with B. velezensis significantly reduced body weight loss and mortality of CRKP-infected mice in the preventive model. The oral administration of B. velezensis in a therapeutic model also decreased the mortality and illness severity in CRKP-infected mice. Moreover, a two-week oral acute toxicity assay in guinea pigs did not reveal any aberrant clinical signs. Our findings demonstrate the potential effectiveness of our candidate probiotic strain, B. velezensis, against CRKP, suggesting that it could be used as an antimicrobial agent for treating CRKP-related infections.