Role of Gardnerella vaginalis in the Pathogenesis of Bacterial Vaginosis: A Conceptual Model

Schwebke, Jane R.; Muzny, Christina A.; Josey, William E.

doi:10.1093/infdis/jiu089

Cited by 213 publications

(185 citation statements)

References 49 publications

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“…These investigators also tested endometrial fluid and tissue for cytokines and defensins and showed that colonization of the upper FRT with low levels of vaginal species is not associated with increased levels of inflammatory markers. Furthermore, Schwebke and colleagues (15,16) hypothesize that G. vaginalis initiates the formation of biofilms composed of diverse anaerobic and microaerophilic bacteria. It is possible that G. vaginalis individually does not induce an overt proinflammatory response; however, it may require the complex polymicrobial community.…”

Section: Discussionmentioning

confidence: 99%

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Human Three-Dimensional Endometrial Epithelial Cell Model To Study Host Interactions with Vaginal Bacteria and Neisseria gonorrhoeae

et al. 2017

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Colonization of the endometrium by pathogenic bacteria ascending from the lower female reproductive tract (FRT) is associated with many gynecologic and obstetric health complications. To study these host-microbe interactions in vitro, we developed a human three-dimensional (3-D) endometrial epithelial cell (EEC) model using the HEC-1A cell line and the rotating wall vessel (RWV) bioreactor technology. Our model, composed of 3-D EEC aggregates, recapitulates several functional/structural characteristics of human endometrial epithelial tissue, including cell differentiation, the presence of junctional complexes/desmosomes and microvilli, and the production of membrane-associated mucins and Toll-like receptors (TLRs). TLR function was evaluated by exposing the EEC aggregates to viral and bacterial products. Treatment with poly(I·C) and flagellin but not with synthetic lipoprotein (fibroblast-stimulating lipoprotein 1 [FSL-1]) or lipopolysaccharide (LPS) significantly induced proinflammatory mediators in a dose-dependent manner. To simulate ascending infection, we infected EEC aggregates with commensal and pathogenic bacteria: Lactobacillus crispatus, Gardnerella vaginalis, and Neisseria gonorrhoeae. All vaginal microbiota and N. gonorrhoeae efficiently colonized the 3-D surface, localizing to crevices of the EEC model and interacting with multiple adjacent cells simultaneously. However, only infection with pathogenic N. gonorrhoeae and not infection with the other bacteria tested significantly induced proinflammatory mediators and significant ultrastructural changes to the host cells. The latter observation is consistent with clinical findings and illustrated the functional specificity of our system. Additionally, we highlighted the utility of the 3-D EEC model for the study of the pathogenesis of N. gonorrhoeae using a well-characterized ΔpilT mutant. Overall, this study demonstrates that the human 3-D EEC model is a robust tool for studying host-microbe interactions and bacterial pathogenesis in the upper FRT.

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Section: Discussionmentioning

confidence: 99%

“…The role of G. vaginalis in BV is still controversial. Schwebke and colleagues hypothesize that G. vaginalis is sexually transmitted and initiates polymicrobial biofilm formation (15,16). Importantly, BV has a high recurrence rate and is difficult to treat (17).…”

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confidence: 99%

Human Three-Dimensional Endometrial Epithelial Cell Model To Study Host Interactions with Vaginal Bacteria and Neisseria gonorrhoeae

et al. 2017

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“…In fact, different hypothesis have been considered to find out the principal trigger of the BV; one of them is the racial and societal differences, in which African American women have a higher probability to contract BV than European women because of their different vaginal pH [7]. Another hypothesis for the BV pathogenesis sees the G. vaginalis as the key-stone pathogen, which through its metabolic pathways and ability to form a biofilm, lowers the reduction-oxidation potential in the vaginal microbiome and then causes a marked decrease in lactobacilli and an increase in BVassociated bacteria [8].…”

Section: Interpretative Criteria Of Vaginal Smearsmentioning

confidence: 99%

Comparison between Nugent's and Hay/Ison scoring criteria for the diagnosis of Bacterial Vaginosis in WASP prepared vaginal samples

Antonucci¹,

Mirandola²,

Fontana³

2017

Clinical-Investigation

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Background: The aim of this study was to compare two different Bacterial Vaginosis diagnosis criteria, Nugent's score system and Hay/Ison criterion, by using Gram-stained vaginal smears. Materials and findings:Gram-stained smears were prepared with 10 µl and 30 µl of 100 vaginal samples, collected in ESwab ® , by the WASP ® automatic system. All smears were examined at 1000X magnification and assessed using both Nugent and Hay/Ison criteria. In addition, the presence of clue cells was recorded. All the slides were assessed by three independent expert readers in a blinded manner. Conclusions:The Hay/Ison criterion is a credible alternative to the Nugent's score system for the diagnosis of Bacterial Vaginosis. Furthermore, the combination of WASP ® automatic system and the Hay/Ison criterion can represent a fast and reliable workflow, especially in those laboratories where the request of vaginal culture tests is extremely high.

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“…BV results from vaginal dysbiosis characterized by a shift in commensal saprophytic vaginal microflora dominated by lactobacilli, to a microflora dominated by facultative and strict anaerobes (Hillier, 1993). While still poorly understood and categorized due to probable multifactorial origins (Reid, 2018), BV is linked in most cases to the presence of Gardnerella vaginalis (Schwebke et al, 2014;Hay, 2017), which can produce a biofilm that is not degraded by antibiotic treatment and that protects the bacteria against antibiotherapy (Thellin et al, 2016). One consequence is that numerous patients suffer from recurrent infections (Bradshaw et al, 2006;Sobel et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Hen egg white lysozyme is less active against Gardnerella vaginalis biofilm than human lysozyme

et al. 2018

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Bacterial vaginosis is a condition that affects millions of women worldwide. In most cases, it can be linked to the presence of Gardnerella vaginalis. Classical metronidazole treatments can lead to recurrence of bacterial vaginosis in more than 50% of cases due to its inability to fully eradicate the infection. This can be due to protective shielding of G. vaginalis by the biofilm it synthesizes. We showed previously that the coadministration of recombinant human lysozyme, as a biofilm-degrading agent, with the antibiotic greatly improves its efficiency in vitro. Lysozyme purified from egg white is less expensive than recombinant human lysozyme and is commonly produced as an additive for human consumption. Our goal was to compare the effects of recombinant human lysozyme with that of egg white lysozyme alongside a conventional antibiotic treatment for bacterial vaginosis, using in vitro vaginal biofilm models. The results obtained here show that recombinant human lysozyme is a more efficient biofilm-degrading agent than egg white lysozyme and therefore constitutes a better choice as an anti-biofilm co-treatment for current vaginal antibiotherapy against G. vaginalis infection.

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Role of Gardnerella vaginalis in the Pathogenesis of Bacterial Vaginosis: A Conceptual Model

Abstract: G. vaginalis is the pathogen responsible for the initiation of BV. Future research should focus on preventing its transmission and improved therapeutics for the biofilm infection that is caused by this pathogen and host anaerobes.

Cited by 213 publications

References 49 publications

Human Three-Dimensional Endometrial Epithelial Cell Model To Study Host Interactions with Vaginal Bacteria and Neisseria gonorrhoeae

Human Three-Dimensional Endometrial Epithelial Cell Model To Study Host Interactions with Vaginal Bacteria and Neisseria gonorrhoeae

Comparison between Nugent's and Hay/Ison scoring criteria for the diagnosis of Bacterial Vaginosis in WASP prepared vaginal samples

Hen egg white lysozyme is less active against Gardnerella vaginalis biofilm than human lysozyme

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