Gardnerella vaginalis and Prevotella bivia Trigger Distinct and Overlapping Phenotypes in a Mouse Model of Bacterial Vaginosis.
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ABSTRACT:
SUBMITTER: Gilbert NM
PROVIDER: S-EPMC6736442 | biostudies-literature | 2019 Aug
REPOSITORIES: biostudies-literature
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Project description:Bacterial vaginosis (BV) is associated with a highly structured polymicrobial biofilm on the vaginal epithelium where Gardnerella species presumably play a pivotal role. Gardnerella vaginalis, Atopobium vaginae, and Prevotella bivia are vaginal pathogens detected during the early stages of incident BV. Herein, we aimed to analyze the impact of A. vaginae and P. bivia on a pre-established G. vaginalis biofilm using a novel in vitro triple-species biofilm model. Total biofilm biomass was determined by the crystal violet method. We also discriminated the bacterial populations in the biofilm and in its planktonic fraction by using PNA FISH. We further analyzed the influence of A. vaginae and P. bivia on the expression of key virulence genes of G. vaginalis by quantitative PCR. In our tested conditions, A. vaginae and P. bivia were able to incorporate into pre-established G. vaginalis biofilms but did not induce an increase in total biofilm biomass, when compared with 48-h G. vaginalis biofilms. However, they were able to significantly influence the expression of HMPREF0424_0821, a gene suggested to be associated with biofilm maintenance in G. vaginalis. This study suggests that microbial relationships between co-infecting bacteria can deeply affect the G. vaginalis biofilm, a crucial marker of BV.
| S-EPMC7924186 | biostudies-literature
Project description:Antibiotic resistance and infection recurrence are critical issues in treating bacterial vaginosis, the most common vaginal disorder in women of reproductive age. Novel alternatives to traditional antibiotics, such as peptidomimetics, have the potential to address this challenge. Previously, two series of cationic amphiphiles (CAms) were developed with both hydrophilic head groups and non-polar domains, giving them the ability to self-assemble into supramolecular nanostructures with membrane-lytic properties. Those CAms were shown to be effective against biofilms of Gardnerella vaginalis while preserving the commensal microbiota. Two new series of CAms were designed with varying levels of flexibility between the hydrophilic head groups and the hydrophobic domains. Activities against the vaginal pathogen G. vaginalis ranged from 1.3 to 18.5 µM, while the tested vaginal lactobacilli were significantly more tolerant of CAms, with minimal inhibitory concentration values as high as 208 µM. Minimal biofilm bactericidal concentrations of the tested CAms ranged from 21.47 to <388.3 µM, and were lowest against resistant forms of G. vaginalis, while Lactobacillus biofilms were tolerant of concentrations ≥687 µM. Safety aspects of the CAms were also investigated, and they were found to be safe for use against vaginal ectocervical tissue.
| S-EPMC7076263 | biostudies-literature
Project description:Bacterial vaginosis (BV) is the most common vaginal infection found in women in the world. Due to increasing drug-resistance of virulent pathogen such as Gardnerella vaginalis (G. vaginalis), more than half of BV patients suffer recurrence after antibotics treatment. Here, metastable iron sulfides (mFeS) act in a Gram-dependent manner to kill bacteria, with the ability to counteract resistant G. vaginalis for BV treatment. With screening of iron sulfide minerals, metastable Fe3 S4 shows suppressive effect on bacterial growth with an order: Gram-variable G. vaginalis >Gram-negative bacteria>> Gram-positive bacteria. Further studies on mechanism of action (MoA) discover that the polysulfide species released from Fe3 S4 selectively permeate bacteria with thin wall and subsequently interrupt energy metabolism by inhibiting glucokinase in glycolysis, and is further synergized by simultaneously released ferrous iron that induces bactericidal damage. Such multiple MoAs enable Fe3 S4 to counteract G. vaginalis strains with metronidazole-resistance and persisters in biofilm or intracellular vacuole, without developing new drug resistance and killing probiotic bacteria. The Fe3 S4 regimens successfully ameliorate BV with resistant G. vaginalis in mouse models and eliminate pathogens from patients suffering BV. Collectively, mFeS represent an antibacterial alternative with distinct MoA able to treat challenged BV and improve women health.
| S-EPMC8981900 | biostudies-literature
Project description:Bacterial vaginosis (BV) is a disease caused by vaginal microbiota dysbiosis. Here, we propose the use of synthetic bacterial consortia transplantation (SBCT) for the treatment of Gardnerella vaginalis-induced BV mice. The results showed that SBCT significantly reduced vaginal tissue damage and restored the vaginal microbiota, decreased the secretion of pro-inflammatory cytokines (IL-1β and IL-8), and suppressed NF-κB activation. IL-17, iNOS, and COX-2 expression in vaginal tissue were also down-regulated. However, IL-10 and Foxp3 showed up-regulated expression in mice. Compared with vaginal microbiota transplantation (VMT), results indicated that VMT was more effective than SBCT in suppressing G. vaginalis-induced inflammation. The obtained results suggest that synthetic bacterial consortia might be used as a potential biotherapeutic agent for the treatment of G. vaginalis-induced bacterial vaginosis. Video Abstract.
| S-EPMC10026434 | biostudies-literature
Project description:BackgroundBacterial 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.MethodsVaginal 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.ResultsG. 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.ConclusionsWe 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.
| S-EPMC5460423 | biostudies-literature
Project description:Bacterial vaginosis (BV) is a recurrent dysbiosis that is frequently associated with preterm birth, increased risk for acquisition of human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs). The overgrowth of a key pathobiont, Gardnerella vaginalis, as a recalcitrant biofilm is central to the development of this dysbiosis. Overgrowth of vaginal biofilms, seeded by initial G. vaginalis colonization, leads to recurrent symptomatic BV which is poorly resolved by classically used antibiotics. In this light, the use of bacteriophages and/or their proteins, represents a promising alternative. Here we identify 84 diverse anti-Gardnerella endolysins across 7 protein families. A subset of 36 endolysin candidates were refactored and overexpressed in an E. coli BL21 (DE3) system and 5 biochemically and structurally diverse endolysins were fully characterized. Each candidate endolysin showed good lytic activity against planktonic G. vaginalis ATCC14018, as well as G. vaginalis clinical isolates. These endolysin candidates were assayed in biofilm prevention and disruption assays, with biofilm disruption at low microgram concentrations (5 μg/ml) observed. In addition to clonal G. vaginalis biofilms, endolysin candidates could also successfully disrupt polyspecies biofilms. Importantly, none of our candidates showed lytic activity against commensal lactobacilli present in the vaginal microbiota such as L. crispatus, L. jensenii, L. gasseri, and L. iners or against Atopobium vaginae (currently classified as Fannyhessa vaginae). The potency and selectivity of these novel endolysins constitute a promising alternative treatment to combat BV, avoiding problems associated with antibiotic resistance, while retaining beneficial commensal bacteria in the vaginal flora. The diverse library of candidates reported here represents a strong repository of endolysins for further preclinical development.
| S-EPMC9018826 | biostudies-literature
Project description: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.
| S-EPMC4481526 | biostudies-literature
Project description:Bacterial vaginosis (BV) is a dysbiosis of the vaginal flora characterized by a shift from a Lactobacillus-dominant environment to a polymicrobial mixture including Actinobacteria and gram-negative bacilli. BV is a common vaginal condition in women and is associated with increased risk of sexually transmitted infection and adverse pregnancy outcomes such as preterm birth. Gardnerella vaginalis is one of the most frequently isolated bacterial species in BV. However, there has been much debate in the literature concerning the contribution of G. vaginalis to the etiology of BV, since it is also present in a significant proportion of healthy women. Here we present a new murine vaginal infection model with a clinical isolate of G. vaginalis. Our data demonstrate that this model displays key features used clinically to diagnose BV, including the presence of sialidase activity and exfoliated epithelial cells with adherent bacteria (reminiscent of clue cells). G. vaginalis was capable of ascending uterine infection, which correlated with the degree of vaginal infection and level of vaginal sialidase activity. The host response to G. vaginalis infection was characterized by robust vaginal epithelial cell exfoliation in the absence of histological inflammation. Our analyses of clinical specimens from women with BV revealed a measureable epithelial exfoliation response compared to women with normal flora, a phenotype that, to our knowledge, is measured here for the first time. The results of this study demonstrate that G. vaginalis is sufficient to cause BV phenotypes and suggest that this organism may contribute to BV etiology and associated complications. This is the first time vaginal infection by a BV associated bacterium in an animal has been shown to parallel the human disease with regard to clinical diagnostic features. Future studies with this model should facilitate investigation of important questions regarding BV etiology, pathogenesis and associated complications.
| S-EPMC3602284 | biostudies-literature
Project description:BackgroundWe aimed to determine the prevalence of vaginal colonization by Gardnerella vaginalis and of bacterial vaginosis (BV) in Portuguese pregnant women, and to identify risk factors for BV and G. vaginalis colonization in pregnancy.MethodsA cross-sectional study was conducted among pregnant women aged ≥ 18 years who were attending in two public hospitals of the Northwest region of Portugal. Epidemiological data was collected by anonymous questionnaire. BV was diagnosed by Nugent criteria and G. vaginalis presence was identified by polymerase chain reaction. Crude associations between the study variables and BV or G. vaginalis colonization were quantified by odds ratios (ORs) and their 95% confidence intervals (CIs).ResultsThe prevalences of BV and of G. vaginalis colonization among Portuguese pregnant women were 3.88% and 67.48%, respectively. Previous preterm delivery and colonization by G. vaginalis were factors with very high OR, but only statistically significant for a 90% CI. Conversely, higher rates of G. vaginalis colonization were found in women with basic educational level (OR = 2.77, 95% CI [1.33-5.78]), during the second trimester of pregnancy (OR = 6.12, 95% CI [1.80-20.85]) and with BV flora (OR = 8.73, 95% CI [0.50-153.60]).DiscussionDespite the lower number of women with BV, prevalence ratios and association with risk factors were similar to recent European studies. However, the percentage of healthy women colonized by G. vaginalis was significantly higher than many previous studies, confirming that G. vaginalis colonization does not always lead to BV development.
| S-EPMC5580382 | biostudies-literature
Project description:Bacterial vaginosis (BV) is a polymicrobial syndrome characterized by a diminished number of protective bacteria in the vaginal flora. Instead, it is accompanied by a significant increase in facultative and strict anaerobes, including Gardnerella vaginalis (G. vaginalis). BV is one of the most common gynecological problems experienced by reproductive age-women. Because an ideal and standard animal model for human BV induced by G. vaginalis is still underdeveloped, the main objective of this study was to develop a mouse model for human BV induced by G. vaginalis to demonstrate the clinical attributes observed in BV patients. A total of 80 female ICR mice were randomly assigned to 4 groups and intravaginally inoculated with different doses of G. vaginalis: NC (uninfected negative control), PC1 (inoculated with 1 × 105 CFU of G. vaginalis), PC2 (inoculated with 1 × 106 CFU of G. vaginalis) and PC3 (inoculated with 1 × 107 CFU of G. vaginalis). The myeloperoxidase (MPO) activity and serum concentrations of cytokines (IL-1β, IL-10) in mice administered with G. vaginalis were significantly higher than those of the control group. Gross lesion and histopathological analysis of reproductive tract of mice inoculated with G. vaginalis showed inflammation and higher epithelial cell exfoliation compared to the control group. In addition, vaginal swabs from the mice inoculated with G. vaginalis showed the presence of clue cells, which are a characteristic feature of human BV. Altogether, our results suggested that G. vaginalis is sufficient to generate comparable clinical attributes seen in patients with BV.
| S-EPMC10536170 | biostudies-literature