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      Bacterial Vaginosis Biofilms: Challenges to Current Therapies and Emerging Solutions

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          Abstract

          Bacterial vaginosis (BV) is the most common genital tract infection in women during their reproductive years and it has been associated with serious health complications, such as preterm delivery and acquisition or transmission of several sexually transmitted agents. BV is characterized by a reduction of beneficial lactobacilli and a significant increase in number of anaerobic bacteria, including Gardnerella vaginalis, Atopobium vaginae, Mobiluncus spp., Bacteroides spp. and Prevotella spp.. Being polymicrobial in nature, BV etiology remains unclear. However, it is certain that BV involves the presence of a thick vaginal multi-species biofilm, where G. vaginalis is the predominant species. Similar to what happens in many other biofilm-related infections, standard antibiotics, like metronidazole, are unable to fully eradicate the vaginal biofilm, which can explain the high recurrence rates of BV. Furthermore, antibiotic therapy can also cause a negative impact on the healthy vaginal microflora. These issues sparked the interest in developing alternative therapeutic strategies. This review provides a quick synopsis of the currently approved and available antibiotics for BV treatment while presenting an overview of novel strategies that are being explored for the treatment of this disorder, with special focus on natural compounds that are able to overcome biofilm-associated antibiotic resistance.

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          Most cited references132

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          Prebiotics: The Concept Revisited

          The Journal of Nutrition, 137(3), 830S-837S
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            The prevalence of bacterial vaginosis in the United States, 2001-2004; associations with symptoms, sexual behaviors, and reproductive health.

            Bacterial vaginosis (BV), a disturbance of vaginal microflora, is a common cause of vaginal symptoms and is associated with an increased risk of acquisition of sexually transmitted infections, HIV, and with adverse pregnancy outcomes. We determined prevalence and associations with BV among a representative sample of women of reproductive age in the United States. Women aged 14-49 years participating in the National Health and Nutrition Examination Survey 2001-2004 were asked to submit a self-collected vaginal swab for Gram staining. BV, determined using Nugent's score, was defined as a score of 7-10. The prevalence of BV was 29.2% (95% confidence interval 27.2%-31.3%) corresponding to 21 million women with BV; only 15.7% of the women with BV reported vaginal symptoms. Prevalence was 51.4% among non-Hispanic blacks, 31.9% among Mexican Americans, and 23.2% among non-Hispanic whites (P <0.01 for each comparison). Although BV was also associated with poverty (P <0.01), smoking (P <0.05), increasing body mass index (chi2 P <0.0001 for trend), and having had a female sex partner (P <0.005), in the multivariate model, BV only remained positively associated with race/ethnicity, increasing lifetime sex partners (chi2 P <0.001 for trend), increasing douching frequency (chi2 P for trend <0.001), low educational attainment (P <0.01), and inversely associated with current use of oral contraceptive pills (P <0.005). BV is a common condition; 84% of women with BV did not report symptoms. Because BV increases the risk of acquiring sexually transmitted infections, BV could contribute to racial disparities in these infections.
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              Adherent biofilms in bacterial vaginosis.

              Bacterial vaginosis is a common infectious disorder. Although known since ancient times, little progress has occurred in identifying causal factors. Our aims were to study the bacterial community structure and the spatial organization of microbiota on the epithelial surfaces of vaginal biopsy specimens. We investigated the composition and spatial organization of bacteria associated with the vaginal epithelium in biopsy specimens from 20 patients with bacterial vaginosis and 40 normal premenopausal and postmenopausal controls using a broad range of fluorescent bacterial group-specific rRNA-targeted oligonucleotide probes. Bacterial vaginosis was associated with greater occurrence and higher concentrations of a variety of bacterial groups. However, only Gardnerella vaginalis developed a characteristic adherent biofilm that was specific for bacterial vaginosis. A biofilm comprised of confluent G vaginalis with other bacterial groups incorporated in the adherent layer is a prominent feature of bacterial vaginosis. II-2.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                20 January 2016
                2015
                : 6
                : 1528
                Affiliations
                [1] 1Laboratory of Research in Biofilms Rosário Oliveira, Centre of Biological Engineering, University of Minho Braga, Portugal
                [2] 2Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto Porto, Portugal
                [3] 3Health Sciences Research Center, Faculty of Health Sciences, University of Beira Interior Covilhã, Portugal
                [4] 4Labfit, Health Products Research and Development Lda Covilhã, Portugal
                [5] 5Child and Woman's Health Department, Centro Hospitalar Cova da Beira Covilhã, Portugal
                Author notes

                Edited by: Johnan A. R. Kaleeba, Uniformed Services University of the Health Sciences, USA

                Reviewed by: Don A Baldwin, Signal Biology, Inc., USA; Elisabeth Margaretha Bik, Stanford University School of Medicine, USA

                *Correspondence: Nuno Cerca nunocerca@ 123456ceb.uminho.pt

                This article was submitted to Infectious Diseases, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2015.01528
                4718981
                26834706
                6f893f5b-0204-4cc8-a4e0-1f7836637ce1
                Copyright © 2016 Machado, Castro, Palmeira-de-Oliveira, Martinez-de-Oliveira and Cerca.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 22 October 2015
                : 18 December 2015
                Page count
                Figures: 0, Tables: 2, Equations: 0, References: 130, Pages: 13, Words: 10390
                Funding
                Funded by: Fundação para a Ciência e a Tecnologia 10.13039/501100001871
                Award ID: UID/BIO/04469/2013
                Award ID: SFRH/BD/87569/2012
                Award ID: SFRH/BD/93963/2013
                Categories
                Public Health
                Mini Review

                Microbiology & Virology
                bacterial vaginosis,biofilms,gardnerella vaginalis,antibiotics,emerging therapies

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