An adherent Gardnerella vaginalis biofilm persists on the vaginal epithelium after standard therapy with oral metronidazole

Swidsinski, Alexander; Mendling, Werner; Loening‐Baucke, Vera; Swidsinski, Sonja; Dörffel, Yvonne; Scholze, Jürgen; Lochs, Herbert; Verstraelen, Hans

doi:10.1016/j.ajog.2007.06.039

Cited by 277 publications

(249 citation statements)

References 29 publications

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“…Indeed, direct evidence from the microscopic analysis of vaginal biopsies of women with BV has revealed the presence of a bacterial biofilm on the vaginal epithelium (Swidsinski et al, 2005). A follow-up study revealed that metronidazole therapy failed to clear the biofilm, and suggested that this was related to relapse (Swidsinski et al, 2008). These studies have revealed biofilm formation as an important virulence determinant in BV.…”

Section: Discussionmentioning

confidence: 99%

Analysis of adherence, biofilm formation and cytotoxicity suggests a greater virulence potential of Gardnerella vaginalis relative to other bacterial-vaginosis-associated anaerobes

et al. 2010

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Worldwide, bacterial vaginosis (BV) is the most common vaginal disorder in women of childbearing age. BV is characterized by a dramatic shift in the vaginal microflora, involving a relative decrease in lactobacilli, and a proliferation of anaerobes. In most cases of BV, the predominant bacterial species found is Gardnerella vaginalis. However, pure cultures of G. vaginalis do not always result in BV, and asymptomatic women are sometimes colonized with low numbers of G. vaginalis. Thus, there is controversy about whether G. vaginalis is an opportunistic pathogen and the causative agent of many cases of BV, or whether BV is a polymicrobial condition caused by the collective effects of an altered microbial flora. Recent studies of the biofilm-forming potential and cytotoxic activity of G. vaginalis have renewed interest in the virulence potential of this organism. In an effort to tease apart the aetiology of this disorder, we utilized in vitro assays to compare three virulence properties of G. vaginalis relative to other BVassociated anaerobes. We designed a viable assay to analyse bacterial adherence to vaginal epithelial cells, we compared biofilm-producing capacities, and we assessed cytotoxic activity. Of the BV-associated anaerobes tested, only G. vaginalis demonstrated all three virulence properties combined. This study suggests that G. vaginalis is more virulent than other BV-associated anaerobes, and that many of the bacterial species frequently isolated from BV may be relatively avirulent opportunists that colonize the vagina after G. vaginalis has initiated an infection. INTRODUCTIONBacterial vaginosis (BV) is the most prevalent vaginal disorder in women of reproductive age, affecting 10-20 % of Caucasian women, and 30-50 % of African American women, although estimates of its prevalence depend on the population studied (Eschenbach, 1993;Sobel, 2000). The normal healthy vagina is populated mainly by hydrogenperoxide-producing lactobacilli that inhibit the growth of other vaginal flora (Eschenbach et al., 1989). BV is characterized by a loss of these protective lactobacilli, an increase in vaginal pH to .4.5, and the proliferation of a variety of anaerobic species. Symptoms of BV can include a thin greyish-white vaginal discharge with a foul odour, and mild irritation. Of more concern is that BV is associated with serious disorders, such as pelvic inflammatory disease (Sobel, 2000;Larsson et al., 2005) and adverse pregnancy outcomes, such as preterm delivery, low birth weight and post-partum endometritis. BV also increases the risk of male-to-female, and female-to-male, HIV transmission (Schmid et al., 2000).Gardnerella vaginalis is present in up to 95 % of cases of BV (Catlin, 1992;Marrazzo et al., 2008); however, with the advancement of molecular tools, it has been shown that the numbers and diversity of anaerobes associated with BV are high (Oakley et al., 2008). One study has found that pure cultures of G. vaginalis do not always cause BV, and that the organism can occur, albeit in low numbers, in healt...

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Section: Discussionmentioning

confidence: 99%

Analysis of adherence, biofilm formation and cytotoxicity suggests a greater virulence potential of Gardnerella vaginalis relative to other bacterial-vaginosis-associated anaerobes

et al. 2010

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“…The ability of lactobacilli to adhere to vaginal epithelial surfaces is believed to be important to allow colonization and host interaction and exclude pathogens (38). The BV-associated microbes, G. vaginalis and Atopobium vaginae, are able to form dense biofilms recalcitrant to standard metronidazole treatment (39,40). However, L. iners AB-1 can interfere with, and displace, G. vaginalis biofilms in vitro, suggesting a role in restoration of a healthy vagina post-BV (41).…”

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confidence: 99%

At the crossroads of vaginal health and disease, the genome sequence of Lactobacillus iners AB-1

Macklaim

Gloor²,

Anukam

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

196

191

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Lactobacilli have long been regarded as important constituents of the healthy human vagina. Lactobacillus iners is the most frequently detected bacterial species in the vagina, but little is known about its characteristics. We report a description of the whole-genome sequence of L. iners AB-1 along with comparative analysis of published genomes of closely related strains of lactobacilli. The genome is the smallest Lactobacillus reported to date, with a 1.3-Mbp single chromosome. The genome seems to have undergone one or more rapid evolution events that resulted in large-scale gene loss and horizontal acquisition of a number of genes for survival in the vagina. L. iners may exhibit specialized adaptation mechanisms to the vaginal environment, such as an iron–sulfur cluster assembly system, and several unique σ factors to regulate gene transcription in this fluctuating environment. A potentially highly expressed homolog of a cholesterol-binding lysin may also contribute to host cell adhesion or act as a defense mechanism against other microbes. Notably, there is a lack of apparent adhesion proteins, but several cell-anchor proteins were identified and may be important for interaction with the host mucosal tissues. L. iners is widely present in healthy females as well as those suffering from bacterial vaginosis or who have undergone antimicrobial therapy, suggesting that it is an important indigenous species of the vagina.

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“…Although many women respond to antibiotics, BV recurs in 11–29% of women at 1 month [52,54,55] and an adherent G . vaginalis biofilm persists after the antibiotic therapy [56]. Bacteria in biofilms respond differently to antibiotic treatment, showing higher resistance, compared with their planktonic counterparts [57–60].…”

Section: Discussionmentioning

confidence: 99%

Bacterial biota of women with bacterial vaginosis treated with lactoferrin: an open prospective randomized trial

Pino

Giunta

Randazzo

et al. 2017

Microbial Ecology in Health and Disease

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Background: Bacterial vaginosis is the most frequent condition associated to the vaginal microbiota imbalance, affecting about the 40–50% of women in the world. Even if antibiotics are effcetive for bacterial vaginosis treatment a long-term recurrence rates, higher than 70%, is recorded. Lactoferrin is an iron-binding glycoprotein with bacteriostatic and bactericidal properties. It owns the ability to protect the host against infection, by binding and regulating the iron needed for the bacterial proliferation.Objective: The present study was an open prospective randomized trial (registration no. SHI-EVE-2014.01) aimed at characterizing the bacterial biota of women affected by bacterial vaginosis (BV) and assessing the effects of two different lactoferrin concentrations (100 mg and 200 mg vaginal pessaries) on the composition and dynamics of the vaginal bacterial biota.Design: Sixty women with BV were recruited and randomized into two groups to receive lactoferrin pessaries for 10 days. Clinical evaluation was based on Amsel criteria and Nugent scores. Culture-dependent methods and Ion Torrent PGM sequencing of the 16S rRNA gene were applied to study in depth the overall structure of the vaginal bacterial biota and its dynamics during the treatment.Results: Vaginal lactoferrin administration modified the vaginal microbiota composition in patients with BV. During treatment, both 100 mg and 200 mg lactoferrin vaginal pessaries significantly decreased the occurrence of bacteria associated with BV, such as Gardnerella, Prevotella, and Lachnospira, and increased the occurrence of Lactobacillus species. The bacterial biota balance was maintained up to 2 weeks after treatment only in women treated with 200 mg lactoferrin pessaries.Conclusions: This study indicates that lactoferrin could be proposed as an alternative therapeutic approach for BV. Our data showed, for the first time, the dominance of Lactobacillus helveticus species during and after vaginal lactoferrin treatment.

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An adherent Gardnerella vaginalis biofilm persists on the vaginal epithelium after standard therapy with oral metronidazole

Cited by 277 publications

References 29 publications

Analysis of adherence, biofilm formation and cytotoxicity suggests a greater virulence potential of Gardnerella vaginalis relative to other bacterial-vaginosis-associated anaerobes

Analysis of adherence, biofilm formation and cytotoxicity suggests a greater virulence potential of Gardnerella vaginalis relative to other bacterial-vaginosis-associated anaerobes

At the crossroads of vaginal health and disease, the genome sequence of Lactobacillus iners AB-1

Bacterial biota of women with bacterial vaginosis treated with lactoferrin: an open prospective randomized trial

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