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Mario Vaneechoutte - One of the best experts on this subject based on the ideXlab platform.

  • gardnerella vaginalis enhances Atopobium vaginae viability in an in vitro model
    Frontiers in Cellular and Infection Microbiology, 2020
    Co-Authors: Mario Vaneechoutte, Joana Vaz De Castro, Piet Cools, Nuno Cerca, A Rosca
    Abstract:

    Bacterial vaginosis (BV) is the most common vaginal infection among women of reproductive age. A hallmark of BV is the presence of a highly structured polymicrobial biofilm on the vaginal epithelium, presumably initiated by facultative anaerobes of the genus Gardnerella, which then becomes a scaffold for other species to adhere to. One of the species often found incorporated in Gardnerella mediated biofilms is Atopobium vaginae. Interestingly, A. vaginae is very rarely found without the presence of Gardnerella. However, not much is known regarding the interactions between A. vaginae and Gardnerella species. This study assessed biological interactions between Gardnerella vaginalis and A. vaginae. In our in vitro model, by using specific Gardnerella and A. vaginae Peptide Nucleic Acid (PNA)-Fluorescence In Situ Hybridization (FISH) probes, we confirmed that A. vaginae was able to incorporate a pre-formed G. vaginalis biofilm, accounting for up to 20% of the total number of biofilm cells. However, our findings showed that almost 92% of A. vaginae cells lost viability after 48 h of mono-species planktonic growth, but were able to maintain viability when co-cultured with Gardnerella or after pre-conditioning with cell-free supernatant of Gardnerella cultures. While the in vitro conditions are very different from the in vivo microenvironment, this study contributes to a better understanding of why A. vaginae vaginal colonization rarely occurs in the absence of Gardnerella. Overall, this highlights the importance of microbial interactions between BV-associated bacteria and demands more studies focused on the polymicrobial bacterial communities found in BV.

  • Gardnerella vaginalis enhances Atopobium vaginae viability in vitro
    2019
    Co-Authors: Castro Joana, Mario Vaneechoutte, Piet Cools, Rosca A., Cerca Nuno
    Abstract:

    Background: Bacterial vaginosis (BV) is a clinical condition characterized by a dramatic shift in the vaginal microflora from the beneficial lactobacilli to a polymicrobial flora, consisting of strictly and facultatively anaerobic bacteria. It is noteworthy that a hallmark of BV is the presence of a highly structured polymicrobial biofilm on the vaginal epithelium, presumably initiated by a facultative anaerobe, Gardnerella vaginalis, which then become a scaffold for other species to adhere. While not much is known about multi- species interactions within BV biofilms, Atopobium vaginae is often associated with G. vaginalis biofilms and is rarely detected without G. vaginalis.This study was supported by the Portuguese Foundation for Science and Technology (FCT) by the funded project PTDC/BIA-MIC/28271/2017, under the scope of COMPETE2020 (POCI-01-0145- FEDER-028271) and by the strategic funding of unit UID/BIO/04469/2019.info:eu-repo/semantics/publishedVersio

  • gardnerella vaginalis enhances Atopobium vaginae viability in vitro
    2019
    Co-Authors: Joana Vaz De Castro, Mario Vaneechoutte, Piet Cools, A Rosca, Nuno Cerca
    Abstract:

    This study was supported by the Portuguese Foundation for Science and Technology (FCT) by the funded project PTDC/BIA-MIC/28271/2017, under the scope of COMPETE2020 (POCI-01-0145- FEDER-028271) and by the strategic funding of unit UID/BIO/04469/2019.

  • a fruitful alliance the synergy between Atopobium vaginae and gardnerella vaginalis in bacterial vaginosis associated biofilm
    Sexually Transmitted Infections, 2016
    Co-Authors: Liselotte Hardy, Vicky Jespers, Lambert Mwambarangwe, Viateur Musengamana, Mario Vaneechoutte, Said Abdellati, Irith De Baetselier, Janneke Van De Wijgert, Tania Crucitti
    Abstract:

    Objectives Bacterial vaginosis (BV) is characterised by a change in the microbial composition of the vagina. The BV-associated organisms outnumber the health-associated Lactobacillus species and form a polymicrobial biofilm on the vaginal epithelium, possibly explaining the difficulties with antibiotic treatment. A better understanding of vaginal biofilm with emphasis on Atopobium vaginae and Gardnerella vaginalis may contribute to a better diagnosis and treatment of BV. Methods To this purpose, we evaluated the association between the presence of both bacteria by fluorescence in situ hybridisation (FISH) and BV by Nugent scoring in 463 vaginal slides of 120 participants participating in a clinical trial in Rwanda. Results A bacterial biofilm was detected in half of the samples using a universal bacterial probe. The biofilm contained A. vaginae in 54.1% and G. vaginalis in 82.0% of the samples. A. vaginae was accompanied by G. vaginalis in 99.5% of samples. The odds of having a Nugent score above 4 were increased for samples with dispersed G. vaginalis and/or A. vaginae present (OR 4.5; CI 2 to 10.3). The probability of having a high Nugent score was even higher when a combination of adherent G. vaginalis and dispersed A. vaginae was visualised (OR 75.6; CI 13.3 to 429.5) and highest when both bacteria were part of the biofilm (OR 119; CI 39.9 to 360.8). Conclusions Our study, although not comprehensive at studying the polymicrobial biofilm in BV, provided a strong indication towards the importance of A. vaginae and the symbiosis of A. vaginae and G. vaginalis in this biofilm. Trial registration number NCT01796613.

  • P07.16 The importance of Atopobium vaginae in bacterial vaginosis-associated biofilm
    Sexually Transmitted Infections, 2015
    Co-Authors: Liselotte Hardy, Vicky Jespers, Lambert Mwambarangwe, Viateur Musengamana, Mario Vaneechoutte, Said Abdellati, Irith De Baetselier, J Van De Wijgert, Tania Crucitti
    Abstract:

    Introduction In case of bacterial vaginosis (BV), lactobacilli are outnumbered by anaerobic bacteria. These bacteria have been described to form a polymicrobial biofilm (“clue cells”) attached to the vaginal epithelium, possibly explaining the decreased sensitivity to antibiotic treatment and the frequent chronicity of BV. A better understanding of this biofilm may contribute to more precise delineation, and consequently to better diagnosis and treatment of BV. We used Fluorescence In Situ Hybridization (FISH) to study the presence of Atopobium vaginae (Av) and Gardnerella vaginalis (Gv) biofilm, in relation to the status of the vaginal microbiome (according to Nugent score). Methods Duplicates of 461 vaginal slides of 120 participants, participating in a contraceptive vaginal ring trial in Rwanda, were evaluated according to Nugent score after Gram staining and by FISH with species-specific probes for Av and Gv. Results In the majority of samples (59.6%) with Nugent score 7–10 (BV diagnosis), a Gv+Av biofilm was visualised by FISH. In these BV samples, 7% had no Gv and Av present, in 9% Gv and/or Av was present but only planktonic, 18.6% had Gv biofilm but no Av present and 5.8% Gv biofilm with Av planktonic only. When Av and/or Gv were planktonic in the vagina and not part of a biofilm, the Nugent score was low, defining a healthy vaginal microbiome. However the probability of having a disturbed vaginal microbiome (Nugent 7–10) was increased (p A. vaginae was part of the biofilm (p Conclusion Our study focusing on Gv and Av, shows that these are two major players in a polymicrobial condition. It confirms the importance of Gv - biofilm in BV and strongly indicates that Av plays an important role in BV-associated biofilm. Disclosure of interest statement This work was supported by European and Developing Countries Clinical Trials Partnerships (EDCTP), by Combined Highly Active Anti-Retroviral Microbicides (CHAARM) and by Dormeur Investment Service. No pharmaceutical grants were received in the development of this study.

Florence Bretelle - One of the best experts on this subject based on the ideXlab platform.

  • screen and treat program by point of care of Atopobium vaginae and gardnerella vaginalis in preventing preterm birth autop trial study protocol for a randomized controlled trial
    Trials, 2015
    Co-Authors: Florence Bretelle, Florence Fenollar, Didier Raoult, Karine Baumstarck, Cecile Fortanier, Jean Francois Cocallemen, Valerie Serazin, Pascal Auquier, Sandrine Loubiere
    Abstract:

    Background: International recommendations in favor of screening for vaginal infection in pregnancy are based on heterogeneous criteria. In most developed countries, the diagnosis of bacterial vaginosis is only recommended for women with high-risk of preterm birth. The Nugent score is currently used, but molecular quantification tools have recently been reported with a high sensitivity and specificity. Their value for reducing preterm birth rates and related complications remains unexplored. This trial was designed to assess the cost-effectiveness of a systematic screen-and-treat program based on a point-of-care technique for rapid molecular diagnosis, immediately followed by an appropriate antibiotic treatment, to detect the presence of abnormal vaginal flora (specifically, Atopobium vaginae and Gardnerella vaginalis) before 20 weeks of gestation in pregnant women in France. We hypothesized that this program would translate into significant reductions in both the rate of preterm births and the medical costs associated with preterm birth. Methods/Design: A multicenter, open-label randomized controlled trial (RCT) will be conducted in which 20 French obstetrics and gynecology centers will recruit eligible pregnant women at less than 20 weeks gestation with singleton pregnancy and with a low-risk factor for preterm birth. Interventions will include a) an experimental group that will receive a systematic rapid screen-and-treat program from a point-of-care analysis using a molecular quantification method and b) a control group that will receive usual care management. Randomization will be in a 1:1 allocation ratio. The primary endpoint that will be assessed over a period of 12 months will be the incremental cost-effectiveness ratio (ICER) expressed as cost per avoided preterm birth before 37 weeks. Secondary endpoints will include ICER per avoided preterm birth before 24, 28 and 32 weeks, obstetrical outcomes, neonatal outcomes, rates of treatment failure and recurrence episodes for positive women. Uncertainty surrounding these estimates will be addressed using nonparametric bootstrapping and represented using cost-effectiveness acceptability curves. A total of 6,800 pregnant women will be included. (Continued on next page)

  • screen and treat program by point of care of Atopobium vaginae and gardnerella vaginalis in preventing preterm birth autop trial study protocol for a randomized controlled trial
    Trials, 2015
    Co-Authors: Florence Bretelle, Florence Fenollar, Didier Raoult, Karine Baumstarck, Cecile Fortanier, Jean Francois Cocallemen, Valerie Serazin, Pascal Auquier, Sandrine Loubiere
    Abstract:

    International recommendations in favor of screening for vaginal infection in pregnancy are based on heterogeneous criteria. In most developed countries, the diagnosis of bacterial vaginosis is only recommended for women with high-risk of preterm birth. The Nugent score is currently used, but molecular quantification tools have recently been reported with a high sensitivity and specificity. Their value for reducing preterm birth rates and related complications remains unexplored. This trial was designed to assess the cost-effectiveness of a systematic screen-and-treat program based on a point-of-care technique for rapid molecular diagnosis, immediately followed by an appropriate antibiotic treatment, to detect the presence of abnormal vaginal flora (specifically, Atopobium vaginae and Gardnerella vaginalis) before 20 weeks of gestation in pregnant women in France. We hypothesized that this program would translate into significant reductions in both the rate of preterm births and the medical costs associated with preterm birth. A multicenter, open-label randomized controlled trial (RCT) will be conducted in which 20 French obstetrics and gynecology centers will recruit eligible pregnant women at less than 20 weeks gestation with singleton pregnancy and with a low-risk factor for preterm birth. Interventions will include a) an experimental group that will receive a systematic rapid screen-and-treat program from a point-of-care analysis using a molecular quantification method and b) a control group that will receive usual care management. Randomization will be in a 1:1 allocation ratio. The primary endpoint that will be assessed over a period of 12 months will be the incremental cost-effectiveness ratio (ICER) expressed as cost per avoided preterm birth before 37 weeks. Secondary endpoints will include ICER per avoided preterm birth before 24, 28 and 32 weeks, obstetrical outcomes, neonatal outcomes, rates of treatment failure and recurrence episodes for positive women. Uncertainty surrounding these estimates will be addressed using nonparametric bootstrapping and represented using cost-effectiveness acceptability curves. A total of 6,800 pregnant women will be included. This appropriate randomized controlled design will provide insight into the cost-effectiveness and therefore the potential cost savings of a rapid screen-and-treat strategy for molecular abnormal vaginal flora in pregnant women. National and international recommendations could be updated based on the findings of this study. ClinicalTrials.gov: NCT02288832 (registration date: 30 October 2014); Eudract: 2014-001559-22.

  • high Atopobium vaginae and gardnerella vaginalis vaginal loads are associated with preterm birth
    Clinical Infectious Diseases, 2015
    Co-Authors: Florence Bretelle, Patrick Rozenberg, Alain Pascal, Romain Favre, Caroline Bohec, Anderson Loundou, Marievictoire Senat, Germain Aissi, Nathalie Lesavre, Julie Brunet
    Abstract:

    BACKGROUND: Bacterial vaginosis is a risk factor for preterm birth. The various conventional methods for its diagnosis are laborious and not easily reproducible. Molecular quantification methods have been reported recently, but the specific risk factors they might identify remain unclear. METHODS: A prospective multicenter national study included pregnant women at risk of preterm birth. A quantitative molecular tool using a specific real-time polymerase chain reaction assay and serial dilutions of a plasmid suspension quantified Atopobium vaginae, Gardnerella vaginalis, lactobacilli, Mycoplasma hominis, and the human albumin gene (for quality control). RESULTS: In 813 pregnancies, high vaginal loads of either or both of A. vaginae and G. vaginalis were associated with preterm birth (hazard ratio [HR], 3.9; 95% confidence interval {CI}, 1.1-14.1; P = .031). A high vaginal load of A. vaginae was significantly associated with shortened time to delivery and therefore pregnancy length. These times were, respectively, 152.2 and 188.2 days (HR, 5.6; 95% CI, 1.5-21.3; P < .001) before 22 weeks, 149.0 and 183.2 days (HR, 2.8; 95% CI, 1.1-8.2; P = .048) before 28 weeks, and 132.6 and 170.4 days (HR, 2.2; 95% CI, 1.1-4.6; P = .033) before 32 weeks. After multivariate analysis, A. vaginae levels ≥10(8) copies/mL remained significantly associated with delivery before 22 weeks of gestation (adjusted HR, 4.7; 95% CI, .2-17.6; P = .014). CONCLUSIONS: High vaginal loads of A. vaginae and G. vaginalis are associated with late miscarriage and prematurity in high-risk pregnancies. A high vaginal load of A. vaginae (DNA level ≥10(8) copies/mL) identifies a population at high risk of preterm birth. Further studies that both screen for and then treat A. vaginae are needed. CLINICAL TRIALS REGISTRATION: NCT00484653.

  • self collected vaginal swabs for the quantitative real time polymerase chain reaction assay of Atopobium vaginae and gardnerella vaginalis and the diagnosis of bacterial vaginosis
    European Journal of Clinical Microbiology & Infectious Diseases, 2012
    Co-Authors: Jean Pierre Ménard, Florence Fenollar, Didier Raoult, L Boubli, Florence Bretelle
    Abstract:

    The aim of this study was to assess the feasibility of using self-collected vaginal specimens for the quantitative real-time polymerase chain reaction (qPCR) assays of bacterial vaginosis (BV)-associated bacteria versus practitioner-collected swabs. A cross-sectional study included 190 pregnant women enrolled before 20 weeks’ gestation from September 2008 to November 2009. Self- and practitioner-collected swabs were taken during the same prenatal visit for each woman, qPCR assays performed for each, and the results compared. The quantification of the human albumin gene was used as an internal control to ensure sampling quality and accurate comparisons. The level of agreement of the qPCR assays for each microorganism was calculated with the Spearman product moment correlation coefficient and the kappa statistic. In all, 370 vaginal samples (185 self- and 185 practitioner-collected swabs) had a narrow range of values for the number of albumin gene copies and a significant correlation coefficient (Spearman’s rho = 0.532; p < 0.001). The agreement between both sampling methods was excellent (Spearman’s rho was 0.748 for Atopobium vaginae, 0.918 for Lactobacillus species, 0.940 for Gardnerella vaginalis; p < 0.001), especially for high concentrations of A. vaginae (≥108 copies/mL; kappa value = 0.973; p < 0.001) and G. vaginalis (≥109 copies/mL; kappa value = 0.903; p < 0.001). This study demonstrates the validity and reliability of self- versus practitioner-collected swabs for the molecular quantification of Lactobacillus species, G. vaginalis, and A. vaginae.

  • high vaginal concentrations of Atopobium vaginae and gardnerella vaginalis in women undergoing preterm labor
    Obstetrics & Gynecology, 2010
    Co-Authors: Jean Pierre Ménard, Florence Fenollar, Chafika Mazouni, Inesse Salemcherif, Didier Raoult, L Boubli, M Gamerre, Florence Bretelle
    Abstract:

    OBJECTIVE:To estimate the relationship between vaginal quantification of the main microorganisms related with bacterial vaginosis and the risk of preterm delivery among women with preterm labor.METHODS:Molecular methods were used to prospectively quantify Lactobacillus species, Gardnerella vaginalis

Rodriguez S De Cordoba - One of the best experts on this subject based on the ideXlab platform.

  • the antimicrobials anacardic acid and curcumin are not competitive inhibitors of gram positive bacterial pathogenic glyceraldehyde 3 phosphate dehydrogenase by a mechanism unrelated to human c5a anaphylatoxin binding
    Frontiers in Microbiology, 2019
    Co-Authors: Sara Gómez, Marta Subias, Sebastián Albertí, J Querolgarcia, G Sanchezbarron, A Gonzalezalsina, V Francohidalgo, Rodriguez S De Cordoba
    Abstract:

    The ubiquitous and highly abundant glycolytic enzyme D-glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is pivotal for the energy and carbon metabolism of most organisms, including human pathogenic bacteria. For bacteria that depend mostly on glycolysis for survival, GAPDH is an attractive target for inhibitor discovery. The availability of high-resolution structures of GAPDH from various pathogenic bacteria is central to the discovery of new antibacterial compounds. We have determined the X-ray crystal structures of two new GAPDH enzymes from Gram-positive bacterial pathogens, Streptococcus pyogenes and Clostridium perfringens. These two structures, and the recent structure of Atopobium vaginae GAPDH, reveal details in the active site that can be exploited for the design of novel inhibitors based on naturally occurring molecules. Two such molecules, anacardic acid and curcumin, have been found to counter bacterial infection in clinical settings, although the cellular targets responsible for their antimicrobial properties remain unknown. We show that both anacardic acid and curcumin inhibit GAPDH from two bacterial pathogens through uncompetitive and non-competitive mechanisms, suggesting GAPDH as a relevant pharmaceutical target for antibacterial development. Inhibition of GAPDH by anacardic acid and curcumin seems to be unrelated to the immune evasion function of pathogenic bacterial GAPDH, since neither natural compound interfere with binding to the human C5a anaphylatoxin.

Hans Verstraelen - One of the best experts on this subject based on the ideXlab platform.

  • RESEARCH ARTICLE Open Access Susceptibility testing of Atopobium vaginae
    2013
    Co-Authors: Guido Lopes, Florian Waser, Hans Verstraelen, Santos Santiago, Mario Vaneechoutte
    Abstract:

    Background: Atopobium vaginae and Gardnerella vaginalis are major markers for bacterial vaginosis. We aimed to determine the MIC and MBC range of the broad-spectrum anti-infective and antiseptic dequalinium chloride for 28 strains, belonging to 4 species of the genus Atopobium, i.e. A. vaginae, A. minutum, A. rimae and A. parvulum. Methods: The MIC was determined with a broth microdilution assay. Results: The MIC and MBC for Atopobium spp. for dequalinium chloride ranged between < 0.0625 and 2 μg/ml. Conclusions: This study demonstrated that dequalinium chloride inhibits and kills clinical isolates of A. vaginae at concentrations similar to those of clindamycin and lower than those of metronidazole. Background Bacterial vaginosis (BV) is a polymicrobial condition whereby the lactobacilli dominated vaginal microflora is overgrown by anaerobes [1], such as Gardnerella vaginalis and Atopobium vaginae [2]. BV is the most common cause of vaginal complaints among women of childbearing age [3]

  • susceptibility testing of Atopobium vaginae for dequalinium chloride
    BMC Research Notes, 2012
    Co-Authors: Guido Lopes Dos Santos Santiago, Hans Verstraelen, Philipp Grob, Florian Waser, Mario Vaneechoutte
    Abstract:

    Background: Atopobium vaginae and Gardnerella vaginalis are major markers for bacterial vaginosis. We aimed to determine the MIC and MBC range of the broad-spectrum anti-infective and antiseptic dequalinium chloride for 28 strains, belonging to 4 species of the genus Atopobium, i.e. A. vaginae, A. minutum, A. rimae and A. parvulum. Methods: The MIC was determined with a broth microdilution assay. Results: The MIC and MBC for Atopobium spp. for dequalinium chloride ranged between < 0.0625 and 2 μg/ml. Conclusions: This study demonstrated that dequalinium chloride inhibits and kills clinical isolates of A. vaginae at concentrations similar to those of clindamycin and lower than those of metronidazole.

  • Gene polymorphisms of Toll-like and related recognition receptors in relation to the vaginal carriage of Gardnerella vaginalis and Atopobium vaginae.
    Journal of reproductive immunology, 2009
    Co-Authors: Hans Verstraelen, Rita Verhelst, Lieve Nuytinck, Kristien Roelens, Els De Meester, Daniella De Vos, Martine Van Thielen, Rudi Rossau, Wim Delva, Ellen De Backer
    Abstract:

    Host genetic factors have previously been found to act as determinants of differential susceptibility to major infectious diseases. It is less clear whether such polymorphisms may also impose on pathogen recognition in mucosal overgrowth conditions such as bacterial vaginosis, an anaerobic overgrowth condition characterised by the presence of a vaginal biofilm consisting of the Gram-positive anaerobes Gardnerella vaginalis and Atopobium vaginae. We selected 34 single nucleotide polymorphisms pertaining to 9 genes involved with Toll-like receptor-mediated pathogen recognition and/or regulation (LBP, CD14, TLR1, TLR2, TLR4, TLR6, MD2, CARD15 and SIGIRR) and assessed in a nested case-control study their putative association with bacterial vaginosis, as diagnosed by Gram staining, and with the vaginal carriage of A. vaginae and G. vaginalis, as determined by species-specific PCR, among 144 pregnant women. Carriage of G. vaginalis during early pregnancy was associated with the -1155A>G substitution in the promoter region of the MD2 gene (p=0.041). The presence of A. vaginae during the first half of the pregnancy was significantly associated with the CD14 intron 2 1342G>T (p=0.039), the TLR1 exon 4 743A>G (p=0.038), and the CARD15 exon 4 14772A>T (p=0.012) polymorphisms, and marginally significantly associated with the LBP exon13 26842C>T (p=0.056), the CD14 promoter -260C>T (p=0.052), and the TLR1 promoter -7202A>G (p=0.062) polymorphisms. However, no association between gene polymorphisms and bacterial vaginosis as such could be documented. Our data suggest that some degree of genetic susceptibility involving pathogen recognition may occur with the key bacterial vaginosis organism, A. vaginae.

  • gene polymorphisms of toll like and related recognition receptors in relation to the vaginal carriage of gardnerella vaginalis and Atopobium vaginae
    Journal of Reproductive Immunology, 2009
    Co-Authors: Hans Verstraelen, Ellen De Backer, Rita Verhelst, Lieve Nuytinck, Kristien Roelens, Els De Meester, Rudi Rossau, Wim Delva, Martine Van Thielen, Mario Vaneechoutte
    Abstract:

    Host genetic factors have previously been found to act as determinants of differential susceptibility to major infectious diseases. It is less clear whether such polymorphisms may also impose on pathogen recognition in mucosal overgrowth conditions such as bacterial vaginosis, an anaerobic overgrowth condition characterised by the presence of a vaginal biofilm consisting of the Grampositive anaerobes Gardnerella vaginalis and Atopobium vaginae. We selected 34 single nucleotide polymorphisms pertaining to 9 genes involved with Toll-like receptor-mediated pathogen recognition and/or regulation (LBP, CD14, TLR1, TLR2, TLR4, TLR6, MD2, CARD15 and SIGIRR) and assessed in a nested case–control study their putative association with bacterial vaginosis, as diagnosed by Gram staining, and with the vaginal carriage of A. vaginae and G. vaginalis, as determined by species-specific PCR, among 144 pregnant women. Carriage of G. vaginalis during early pregnancy was associated with the −1155A > G substitution in the promoter region of the MD2 gene (p = 0.041). The presence of A. vaginae during the first half of the pregnancy was significantly associated with the CD14 intron 2 1342G > T (p = 0.039), the TLR1 exon 4 743A >G (p = 0.038), and the CARD15 exon 4 14772A > T (p = 0.012) polymorphisms, and marginally significantly associated with the LBP exon13 26842C > T (p = 0.056), the CD14 promoter −260C > T (p = 0.052), and the TLR1 promoter −7202A > G (p = 0.062) polymorphisms. However, no association between gene polymorphisms and bacterial vaginosis as such could be documented. Our data suggest that some degree of genetic susceptibility involving pathogen recognition may occur with the key bacterial vaginosis organism, A. vaginae. © 2009 Elsevier Ireland Ltd. All rights reserved.

  • an adherent gardnerella vaginalis biofilm persists on the vaginal epithelium after standard therapy with oral metronidazole
    American Journal of Obstetrics and Gynecology, 2008
    Co-Authors: Alexander Swidsinski, Werner Mendling, Vera Loeningbaucke, Sonja Swidsinski, Yvonne Dorffel, Jurgen Scholze, Herbert Lochs, Hans Verstraelen
    Abstract:

    Objective The purpose of this study was to determine the efficacy of standard treatment with oral metronidazole in the eradication of the bacterial vaginosis biofilm. Study Design We conducted an interventional follow-up study in which 18 patients with bacterial vaginosis were treated with oral metronidazole during 1 week and subsequently had a single random follow-up assessment at 1-week intervals, up to 5 weeks, with 3 patients representing each point in time. Follow-up assessment included conventional scoring of the vaginal microflora and determination of bacterial biofilm characteristics on a vaginal biopsy through bacterial 16/23S recombinant DNA–based fluorescence in-situ hybridization. Results Although all patients recovered, we consistently observed the resurgence with treatment cessation of a dense and active bacterial biofilm on the vaginal mucosa, primarily consisting of Gardnerella vaginalis and Atopobium vaginae . Conclusion A large reservoir of the core bacteria to bacterial vaginosis persists as a biofilm after metronidazole treatment.

Sara Gómez - One of the best experts on this subject based on the ideXlab platform.

  • Data_Sheet_1_The Antimicrobials Anacardic Acid and Curcumin Are Not-Competitive Inhibitors of Gram-Positive Bacterial Pathogenic Glyceraldehyde-3-Phosphate Dehydrogenase by a Mechanism Unrelated to Human C5a Anaphylatoxin Binding.PDF
    2019
    Co-Authors: Sara Gómez, Javier Querol-garcía, Gara Sánchez-barrón, Marta Subias, Àlex González-alsina, Virginia Franco-hidalgo, Sebastián Albertí, Santiago Rodríguez De Córdoba, Francisco J. Fernández, Cristina M. Vega
    Abstract:

    The ubiquitous and highly abundant glycolytic enzyme D-glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is pivotal for the energy and carbon metabolism of most organisms, including human pathogenic bacteria. For bacteria that depend mostly on glycolysis for survival, GAPDH is an attractive target for inhibitor discovery. The availability of high-resolution structures of GAPDH from various pathogenic bacteria is central to the discovery of new antibacterial compounds. We have determined the X-ray crystal structures of two new GAPDH enzymes from Gram-positive bacterial pathogens, Streptococcus pyogenes and Clostridium perfringens. These two structures, and the recent structure of Atopobium vaginae GAPDH, reveal details in the active site that can be exploited for the design of novel inhibitors based on naturally occurring molecules. Two such molecules, anacardic acid and curcumin, have been found to counter bacterial infection in clinical settings, although the cellular targets responsible for their antimicrobial properties remain unknown. We show that both anacardic acid and curcumin inhibit GAPDH from two bacterial pathogens through uncompetitive and non-competitive mechanisms, suggesting GAPDH as a relevant pharmaceutical target for antibacterial development. Inhibition of GAPDH by anacardic acid and curcumin seems to be unrelated to the immune evasion function of pathogenic bacterial GAPDH, since neither natural compound interfere with binding to the human C5a anaphylatoxin.

  • the antimicrobials anacardic acid and curcumin are not competitive inhibitors of gram positive bacterial pathogenic glyceraldehyde 3 phosphate dehydrogenase by a mechanism unrelated to human c5a anaphylatoxin binding
    Frontiers in Microbiology, 2019
    Co-Authors: Sara Gómez, Marta Subias, Sebastián Albertí, J Querolgarcia, G Sanchezbarron, A Gonzalezalsina, V Francohidalgo, Rodriguez S De Cordoba
    Abstract:

    The ubiquitous and highly abundant glycolytic enzyme D-glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is pivotal for the energy and carbon metabolism of most organisms, including human pathogenic bacteria. For bacteria that depend mostly on glycolysis for survival, GAPDH is an attractive target for inhibitor discovery. The availability of high-resolution structures of GAPDH from various pathogenic bacteria is central to the discovery of new antibacterial compounds. We have determined the X-ray crystal structures of two new GAPDH enzymes from Gram-positive bacterial pathogens, Streptococcus pyogenes and Clostridium perfringens. These two structures, and the recent structure of Atopobium vaginae GAPDH, reveal details in the active site that can be exploited for the design of novel inhibitors based on naturally occurring molecules. Two such molecules, anacardic acid and curcumin, have been found to counter bacterial infection in clinical settings, although the cellular targets responsible for their antimicrobial properties remain unknown. We show that both anacardic acid and curcumin inhibit GAPDH from two bacterial pathogens through uncompetitive and non-competitive mechanisms, suggesting GAPDH as a relevant pharmaceutical target for antibacterial development. Inhibition of GAPDH by anacardic acid and curcumin seems to be unrelated to the immune evasion function of pathogenic bacterial GAPDH, since neither natural compound interfere with binding to the human C5a anaphylatoxin.

  • crystal structure of glyceraldehyde 3 phosphate dehydrogenase from the gram positive bacterial pathogen a vaginae an immunoevasive factor that interacts with the human c5a anaphylatoxin
    Frontiers in Microbiology, 2017
    Co-Authors: J Querolgarcia, Sara Gómez, Sebastián Albertí, Francisco J. Fernández, V Francohidalgo, Ana V Marin, Daniel Fulla, Cecilia Melchortafur, Jordi Juanhuix, Santiago Rodríguez De Córdoba
    Abstract:

    The Gram-positive anaerobic human pathogenic bacterium Atopobium vaginae causes most of the cases of bacterial vaginosis and opportunistic infections in immunocompromised patients. In addition to its well-established role in carbohydrate metabolism, D-glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from Streptococcus pyogenes and S. pneumoniae have been reported to act as an extracellular virulence factor during streptococcal infections. Here, we report the crystal structure of GAPDH from A. vaginae (AvGAPDH) at 2.19 A resolution. The refined model has a crystallographic Rfree of 22.6%. AvGAPDH is a homotetramer wherein each subunit is bound to a nicotinamide adenine dinucleotide (NAD+) molecule. The AvGAPDH enzyme fulfills essential glycolytic as well as moonlight (non-glycolytic) functions, both of which might be targets of chemotherapeutic intervention. We report that AvGAPDH interacts in vitro with the human C5a anaphylatoxin and inhibits C5a-specific neutrophil chemotaxis, thereby suggesting the participation of AvGAPDH in complement-targeted immunoevasion in a context of infection. The availability of high-quality structures of AvGAPDH and other homologous virulence factors from Gram-positive pathogens is critical for drug discovery programs. In this study, sequence and structural differences between AvGAPDH and related bacterial and eukaryotic GAPDH enzymes are reported in an effort to understand how to subvert the immunoevasive properties of GAPDH and evaluate the potential of AvGAPDH as a druggable target.