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We investigated the presence, density and bacterial composition of contraceptive vaginal ring biomass and its association with the vaginal microbiome. Of 415 rings worn by 120 Rwandese women for three weeks, the biomass density was assessed with crystal violet and the bacterial composition of biomass eluates was assessed with quantitative polymerase chain reaction (qPCR). The biomass was visualised after fluorescence in situ hybridisation (FISH) and with scanning electron microscopy (SEM). The vaginal microbiome was assessed with Nugent scoring and vaginal biofilm was visualised after FISH. All vaginal rings were covered with biomass (mean optical density (OD) of 3.36; standard deviation (SD) 0.64). Lactobacilli were present on 93% of the rings, Gardnerella vaginalis on 57%, and Atopobium vaginae on 37%. The ring biomass density was associated with the concentration of A. vaginae (OD +0.03; 95% confidence interval (CI) 0.01-0.05 for one log increase; p = 0.002) and of G. vaginalis (OD +0.03; (95% CI 0.01-0.05; p = 0.013). The density also correlated with Nugent score: rings worn by women with a BV Nugent score (mean OD +0.26), and intermediate score (mean OD +0.09) had a denser biomass compared to rings worn by participants with a normal score (p = 0.002). Furthermore, presence of vaginal biofilm containing G. vaginalis (p = 0.001) and A. vaginae (p = 0.005) correlated with a denser ring biomass (mean OD +0.24 and +0.22 respectively). With SEM we observed either a loose network of elongated bacteria or a dense biofilm. We found a correlation between vaginal dysbiosis and the density and composition of the ring biomass, and further research is needed to determine if these relationships are causal. As multipurpose vaginal rings to prevent pregnancy, HIV, and other sexually transmitted diseases are being developed, the potential impact of ring biomass on the vaginal microbiota and the release of active pharmaceutical ingredients should be researched in depth.

Bacterial vaginosis (BV) is the most common cause of vaginal discharge. It is associated with an increased risk of preterm delivery, pelvic inflammatory disease, and an increased risk of acquisition of sexually transmitted infections including human immunodeficiency virus (HIV). The epidemiology of BV supports sexual transmission. However, its etiology remains unknown. At the center of the debate is whether BV is caused by a primary pathogen or a polymicrobial consortium of microorganisms that are sexually transmitted. We previously published a conceptual model hypothesizing that BV is initiated by sexual transmission of Gardnerella vaginalis. Critics of this model have iterated that G. vaginalis is found in virginal women and in sexually active women with a normal vaginal microbiota. In addition, colonization does not always lead to BV. However, recent advances in BV pathogenesis research have determined the existence of 13 different species within the genus Gardnerella. It may be that healthy women are colonized by nonpathogenic Gardnerella species, whereas virulent strains are involved in BV development. Based on our results from a recent prospective study, in addition to an extensive literature review, we present an updated conceptual model for the pathogenesis of BV that centers on the roles of virulent strains of G. vaginalis, as well as Prevotella bivia and Atopobium vaginae.

The well-known genotypic and phenotypic diversity of G. vaginalis resulted in its classification into at least four subgroups (clades) with diverse genomic properties. To evaluate the virulence potential of G. vaginalis subgroups, we analyzed the virulence-related phenotypic characteristics of 14 isolates of clade 1, 12 isolates of clade 2, 8 isolates of clade 4 assessing their in vitro ability to grow as a biofilm, produce the toxin vaginolysin, and express sialidase activity. Significant differences in VLY production were found (p = 0.023), but further analysis of clade pairs did not confirm this finding. The amount of biofim did not differ significantly among the clades. Analysis of sialidase activity indicated statistically significant differences among the clades (p < 0.001). Production of active recombinant G. vaginalis sialidase demonstrated the link between the sld gene and enzymatic activity, which may be differentially regulated at the transcriptional level. Statistical classification analysis (random forests algorithm) showed that G. vaginalis clades could be best defined by the profiles of two phenotypic characteristics: sialidase activity and vaginolysin production. The results of principal component analysis and hierarchical clustering suggested that all isolates can be subgrouped into three clusters, the structures of which are determined based on phenotypic characteristics of the isolates. Clade 4 was the most homogenous group, as all isolates were found in the same cluster, which is characterized by low production of all studied virulence factors. Clade 2 isolates were mainly distributed between two clusters, whereas clade 1 isolates were found in all three clusters that were characterized by a distinct profile of phenotypic characteristics. Our findings suggest that G. vaginalis subgroups with different virulence potential might play distinct roles in vaginal microbiota.

Bacterial vaginosis (BV), a condition defined by increased vaginal discharge without significant inflammation, is characterized by a change in the bacterial composition of the vagina. Lactobacillus spp., associated with a healthy vaginal microbiome, are outnumbered by BV-associated organisms. These bacteria could form a polymicrobial biofilm which allows them to persist in spite of antibiotic treatment. In this study, we examined the presence of Gardnerella vaginalis and Atopobium vaginae in vaginal biofilms using Peptide Nucleic Acid (PNA) probes targeting these bacteria. For this purpose, we developed three new PNA probes for A. vaginae. The most specific A. vaginae probe, AtoITM1, was selected and then used in an assay with two existing probes, Gard162 and BacUni-1, to evaluate multiplex FISH on clinical samples. Using quantitative polymerase chain reaction (qPCR) as the gold standard, we demonstrated a sensitivity of 66.7% (95% confidence interval: 54.5% - 77.1%) and a specificity of 89.4% (95% confidence interval: 76.1% - 96%) of the new AtoITM1 probe. FISH enabled us to show the presence of a polymicrobial biofilm in bacterial vaginosis, in which Atopobium vaginae is part of a Gardnerella vaginalis-dominated biofilm. We showed that the presence of this biofilm is associated with high bacterial loads of A. vaginae and G. vaginalis.

Gardnerella vaginalis is the most frequently identified bacterium in approximately 95% of bacterial vaginosis (BV) cases. This species often exhibits resistance to multiple antibiotics, posing challenges for treatment. Therefore, there is an urgent need to develop and explore alternative therapeutic strategies for managing bacterial vaginosis. The objective of this study was to identify virulence factors and potential drug targets against Gardnerella vaginalis by utilizing in silico methods, including subtractive and comparative genomics. These methods enabled the systematic comparison of genetic sequences to pinpoint specific features unique to G. vaginalis and crucial for its pathogenicity, which could then inform the development of targeted therapeutic strategies. The analysis of the pathogen's proteomic data aimed to identify proteins that fulfilled specific criteria. These included being non-homologous to human proteins, essential for bacterial survival, amenable to drug targeting, involved in virulence, and contributing to antibiotic resistance. Following these analyses and an extensive literature review, the phospho-2-dehydro-3-deoxyheptonate aldolase enzyme emerged as a promising drug target. To deepen our understanding of the biological function of the identified protein, comprehensive protein structural modeling, validation studies, and network topology analyses were conducted. The subsequent structural analysis, encompassing modeling, validation, and network topology assessment, is aimed at further characterizing the protein. Using a library of around 9,000 FDA-approved compounds from the DrugBank database, a virtual screening was conducted to identify potential compounds that could effectively target the proposed drug target. This approach facilitated the evaluation of existing drugs for their ability to inhibit the target, potentially offering an efficient pathway for developing new treatments against the pathogen. Leveraging the established efficacy, safety, pharmacokinetics, and pharmacodynamics of these compounds, the study suggests repurposing them for Gardnerella vaginalis infections. Among the screened compounds, five specific agents—DB03332, DB07452, DB01262, DB02076, and DB00727—were identified as cost-effective therapeutic options for treating infections related to Gardnerella vaginalis . These compounds were selected based on their efficacy in targeting the pathogen while maintaining economic feasibility. While the results indicate potential efficacy in treating infections caused by the pathogen, further experimental studies are essential to validate these findings.

Background Bacterial vaginosis (BV) is one of the leading causes of vaginal complaints among women of childbearing age. The role of Gardnerella vaginalis remains controversial due to its presence in healthy and BV-type vaginal microflora. The phenotypic and genotypic heterogeneity of G. vaginalis suggested the existence of strain variants linked with different health conditions. We sought to analyze prevalence and distribution of G. vaginalis subgroups (clades) in BV-positive ( n = 29), partial BV ( n = 27), and BV-negative ( n = 53) vaginal samples from Lithuanian women. Methods Vaginal samples were characterized by Amsel criteria and the Nugent method. Bacterial signatures characteristic of BV and concomitant infections were identified by culture and PCR. Using singleplex PCR assays, G. vaginalis subgroups were identified in 109 noncultured vaginal specimens by targeting clade-specific genes. Isolated G. vaginalis clinical strains were subtyped and the presence of the sialidase coding gene was detected by PCR. Data analysis was performed using GraphPad Prism statistical software. Results G. vaginalis was found in 87% of women without BV. Clade 4 was most frequently detected (79.4%), followed by clade 1 (63.7%), clade 2 (42.2%), and clade 3 (15.7%). Multi-clade G. vaginalis communities showed a positive association with Nugent score (NS) ≥ 4 (OR 3.64; 95% CI 1.48–8.91; p = 0.005). Clade 1 and clade 2 were statistically significantly more common in samples with NS 7–10 (OR 4.69; 95% CI 1.38–15.88; p = 0.01 and OR 6.26; 95% CI 2.20–17.81; p ≤ 0.001, respectively). Clade 3 and clade 4 showed no association with high NS (OR 0.88; 95% CI 0.26–3.04; p = 1.00 and OR 1.31; 95% CI 0.39–4.41; p = 0.767, respectively). The gene coding for sialidase was detected in all isolates of clade 1 and clade 2, but not in clade 4 isolates. Conclusions We showed an association between the microbial state of vaginal microflora and specific subgroups of G. vaginalis , the distribution of which may determine the clinical manifestation of BV. The frequent detection of clade 4 in the BV-negative samples might be due its lack of the gene coding for sialidase.

In April 2015, the Division of Microbiology and Infectious Diseases of the National Institute of Allergy and Infectious Diseases hosted an experts technical consultation on bacterial vaginosis (BV), where data regarding controversies over the pathogenesis of BV were discussed. The discussion on the epidemiology and pathogenesis of BV is presented here, and several hypotheses on its pathogenesis are critiqued. Rigorous hypothesis-driven studies are needed to ultimately determine the cause of BV. This information is vital for the prevention and control of this important infection and its adverse public health consequences.

Gardnerella vaginalis is the most common species found in bacterial vaginosis (BV). However, it is also present in a significant proportion of healthy women and G. vaginalis vaginal colonization does not always lead to BV. In an effort to better understand the differences between G. vaginalis isolated from women with a positive (BV) versus a negative (non-BV) diagnosis of BV, we compared the virulence potential of 7 BV and 7 non-BV G. vaginalis isolates and assessed the virulence factors related to biofilm formation, namely: initial adhesion and cytotoxic effect, biofilm accumulation, susceptibility to antibiotics and transcript levels of the known vaginolysin and sialidase genes. Furthermore, we also determined the ability of G. vaginalis to displace lactobacilli previously adhered to HeLa cells. Our results showed that non-BV strains were less virulent than BV strains, as suggested by the lower cytotoxicity and initial adhesion to Hela cells. Significant differences in expression of known virulence genes were also detected, further suggesting a higher virulence potential of the BV associated G. vaginalis . Importantly, we demonstrated that BV associated G. vaginalis were able to displace pre-coated vaginal protective lactobacilli and we hypothesize this to be a trigger for BV development.

Worldwide interest in the use of functional foods containing probiotic bacteria such as Lactobacillus and Bifidobacterium for health promotion and disease prevention has increased significantly. Probiotics have demonstrated beneficial properties including strengthening the body’s natural defense system, inhibiting the growth of pathogenic bacteria, and regulating mental activity, but their effects on the human vagina have not been fully elucidated. The primary purpose of our study was to isolate Lactobacillus strains from old yogurt, a traditional dairy product, and investigate their probiotic potential with respect to the human vaginal system. Four Lactobacillus plantarum (L. plantarum) strains, named ZX1, ZX2, ZX27, and ZX69, were isolated from the yogurt samples. Simultaneously, we used a commercial Lactobacillus strain (Lactobacillus delbrueckii DM8909) as a control strain. We tested the antimicrobial activity of Lactobacillus isolates against Escherichia coli and Gardnerella vaginalis by agar spot and well diffusion tests. Then, we tested the antibiotic susceptibility of the 5 strains by using the minimal inhibitory concentration method. We attempted to detect possible bacteriocin genes by PCR sequencing technique. Using a chemically defined medium simulating genital tract secretions, we found that the selected Lactobacillus strains could alter the expression of known virulence genes in Gardnerella vaginalis. Bacteriocins derived from these isolated strains had potent antibacterial activity against G. vaginalis and E. coli, with the most effective activity observed in the case of ZX27. In addition, all strains including the L. delbrueckii DM8909 were positive for the presence of the plantaricin cluster of genes described in L. plantarum C11. The tested stains possessed the pln gene indicating that one of the antibacterial agents was plantaricin. We assume that the production of antimicrobial substances such as bacteriocins induce G. vaginalis to upregulate antimicrobial resistance genes. The new isolated strains have bacteriocin-related genes and can change the antimicrobial resistance gene transcription of G. vaginalis.

Gardnerella vaginalis is described as a common vaginal bacterial species whose presence correlates strongly with bacterial vaginosis (BV). Here we report the genome sequencing and comparative analyses of three strains of G. vaginalis. Strains 317 (ATCC 14019) and 594 (ATCC 14018) were isolated from the vaginal tracts of women with symptomatic BV, while Strain 409-05 was isolated from a healthy, asymptomatic individual with a Nugent score of 9. Substantial genomic rearrangement and heterogeneity were observed that appeared to have resulted from both mobile elements and substantial lateral gene transfer. These genomic differences translated to differences in metabolic potential. All strains are equipped with significant virulence potential, including genes encoding the previously described vaginolysin, pili for cytoadhesion, EPS biosynthetic genes for biofilm formation, and antimicrobial resistance systems, We also observed systems promoting multi-drug and lantibiotic extrusion. All G. vaginalis strains possess a large number of genes that may enhance their ability to compete with and exclude other vaginal colonists. These include up to six toxin-antitoxin systems and up to nine additional antitoxins lacking cognate toxins, several of which are clustered within each genome. All strains encode bacteriocidal toxins, including two lysozyme-like toxins produced uniquely by strain 409-05. Interestingly, the BV isolates encode numerous proteins not found in strain 409-05 that likely increase their pathogenic potential. These include enzymes enabling mucin degradation, a trait previously described to strongly correlate with BV, although commonly attributed to non-G. vaginalis species. Collectively, our results indicate that all three strains are able to thrive in vaginal environments, and therein the BV isolates are capable of occupying a niche that is unique from 409-05. Each strain has significant virulence potential, although genomic and metabolic differences, such as the ability to degrade mucin, indicate that the detection of G. vaginalis in the vaginal tract provides only partial information on the physiological potential of the organism.