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  • 1
    Language: English
    In: The Journal of infectious diseases, 15 May 2013, Vol.207(10), pp.1491-7
    Description: Bacterial vaginosis is a highly prevalent and poorly understood polymicrobial disorder of the vaginal microbiota, with significant adverse sequelae. Gardnerella vaginalis predominates in bacterial vaginosis. Biofilms of G. vaginalis are present in human infections and are implicated in persistent disease, treatment failure, and transmission. Here we demonstrate that G. vaginalis biofilms contain extracellular DNA, which is essential to their structural integrity. Enzymatic disruption of this DNA specifically inhibits biofilms, acting on both newly forming and established biofilms. DNase liberates bacteria from the biofilm to supernatant fractions and potentiates the activity of metronidazole, an antimicrobial agent used in the treatment of bacterial vaginosis. Using a new murine vaginal colonization model for G. vaginalis, we demonstrate 〉10-fold inhibition of G. vaginalis colonization by DNase. We conclude that DNase merits investigation as a potential nonantibiotic adjunct to existing bacterial vaginosis therapies in order to decrease the risk of chronic infection, recurrence, and associated morbidities.
    Keywords: Biofilms -- Growth & Development ; Deoxyribonucleases -- Metabolism ; Gardnerella Vaginalis -- Physiology ; Vaginosis, Bacterial -- Drug Therapy
    ISSN: 00221899
    E-ISSN: 1537-6613
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  • 2
    Language: English
    In: Pediatrics, 02/2016, Vol.137(Supplement 3), pp.505A-505A
    ISSN: 0031-4005
    E-ISSN: 1098-4275
    Source: CrossRef
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  • 3
    Language: English
    In: The Journal of Bacteriology, 2011, Vol. 193(5), p.1034
    Description: Lactobacillus iners is a common constituent of the human vaginal microbiota. This species was only recently characterized due to its fastidious growth requirements and has been hypothesized to play a role in the pathogenesis of bacterial vaginosis. Here we present the identification and molecular characterization of a protein toxin produced by L. iners. The L. iners genome encodes an open reading frame with significant primary sequence similarity to intermedilysin (ILY; 69.2% similarity) and vaginolysin (VLY; 68.4% similarity), the cholesterol-dependent cytolysins from Streptococcus intermedius and Gardnerella vaginalis, respectively. Clinical isolates of L. iners produce this protein, inerolysin (INY), during growth in vitro, as assessed by Western analysis. INY is a pore-forming toxin that is activated by reducing agents and inhibited by excess cholesterol. It is active across a pH range of 4.5 to 6.0 but is inactive at pH 7.4. At sublytic concentrations, INY activates p38 mitogen-activated protein kinase and allows entry of fluorescent phalloidin into the cytoplasm of epithelial cells. Unlike VLY and ILY, which are human specific, INY is active against cells from a broad range of species. INY represents a new target for studies directed at understanding the role of L. iners in states of health and disease at the vaginal mucosal surface. doi: 10.1128/JB.00694-10
    Keywords: Microorganisms -- Genetic Aspects ; Cholesterol -- Genetic Aspects ; Lactobacillus -- Genetic Aspects ; Bacterial Genetics -- Research;
    ISSN: 0021-9193
    ISSN: 00219193
    E-ISSN: 10985530
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  • 4
    Language: English
    In: American Journal of Obstetrics and Gynecology, 2011, Vol.204(1), pp.41.e1-41.e9
    Description: Recent data suggest vitamin D deficiency (VDD) is associated with bacterial vaginosis (BV) during pregnancy. We hypothesized that VDD is a risk factor for BV in nonpregnant women. Using National Health and Nutrition Examination Survey data, we conducted multivariable logistic regression analyses stratified by pregnancy. VDD was associated with BV only in pregnant women (adjusted odds ratio [AOR], 2.87; 95% confidence interval [CI], 1.13–7.28). Among nonpregnant women, douching (AOR, 1.72; 95% CI, 1.25–2.37), smoking (AOR, 1.66; 95% CI, 1.23–2.24), and black race (AOR, 2.41; 95% CI, 1.67–3.47) were associated with BV; oral contraceptive use was inversely associated with BV (AOR, 0.60; 95% CI, 0.40–0.90). VDD moderated the association between smoking and BV in nonpregnant women. Risk factors for BV differ by pregnancy status. VDD was a modifiable risk factor for BV among pregnant women; evaluation of vitamin D supplementation for prevention or adjunct therapy of BV in pregnancy is warranted.
    Keywords: Bacterial Vaginosis ; National Health and Nutrition Examination Survey ; Pregnancy ; Smoking ; Vitamin D ; Medicine
    ISSN: 0002-9378
    E-ISSN: 1097-6868
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  • 5
    Language: English
    In: American Journal of Obstetrics and Gynecology, January 2016, Vol.214(1), pp.S11-S12
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2015.10.038 Byline: Emilie Vander Haar, Cynthia Gyamfi-Bannerman, Tara M. Randis Author Affiliation: (1) Columbia University Medical Center, New York, NY
    Keywords: Medicine
    ISSN: 0002-9378
    E-ISSN: 1097-6868
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  • 6
    In: The Journal of Infectious Diseases, 2017, Vol. 216(6), pp.744-751
    Description: Abstract Background Streptococcus agalactiae (group B Streptococcus [GBS]) is an important neonatal pathogen and emerging cause of disease in adults. The major risk factor for neonatal disease is maternal vaginal colonization. However, little is known about the relationship between GBS and vaginal microbiota. Methods Vaginal lavage samples from nonpregnant women were tested for GBS, and amplicon-based sequencing targeting the 16S ribosomal RNA V3–V4 region was performed. Results Four hundred twenty-eight of 432 samples met the high-quality read threshold. There was no relationship between GBS carriage and demographic characteristics, α-diversity, or overall vaginal microbiota community state type (CST). Within the non-Lactobacillus-dominant CST IV, GBS positive status was significantly more prevalent in CST IV-A than CST IV-B. Significant clustering by GBS status was noted on principal coordinates analysis, and 18 individual taxa were found to be significantly associated with GBS carriage by linear discriminant analysis. After adjusting for race/ethnicity, 4 taxa were positively associated with GBS, and 6 were negatively associated. Conclusions Vaginal microbiota CST and α-diversity are not related to GBS status. However, specific microbial taxa are associated with colonization of this important human pathogen, highlighting a potential role for the microbiota in promotion or inhibition of GBS colonization.
    Keywords: Group B ; Vaginal Microbiome ; Neonatal Pathogens
    ISSN: 0022-1899
    E-ISSN: 1537-6613
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  • 7
    Language: English
    In: PLoS ONE, 01 January 2013, Vol.8(3), p.e59091
    Description: Group B Streptococcus (GBS; Streptococcus agalactiae) is a major human pathogen that disproportionately affects neonates and women in the peripartum period and is an emerging cause of infection in older adults. The primary toxin of GBS, β-hemolysin/cytolysin (βH/C), has a well-defined role...
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 8
    In: Journal of Antimicrobial Chemotherapy, 2012, Vol. 67(12), pp.2870-2872
    Description: Retrocyclins are cyclic antimicrobial peptides that have been shown to be both broadly active and safe in animal models. RC-101, a synthetic retrocyclin, targets important human pathogens and is a candidate vaginal microbicide. Its activity against microbes associated with bacterial vaginosis is unknown. We investigated the effect of RC-101 on toxin activity, bacterial growth and biofilm formation of Gardnerella vaginalis in vitro. RC-101 potently inhibits the cytolytic activity of vaginolysin, the Gardnerella vaginalis toxin, on both erythrocytes and nucleated cells. RC-101 lacks inhibitory activity against planktonic G. vaginalis but markedly decreases biofilm formation. These dual properties, toxin inhibition and biofilm retardation, justify further exploration of RC-101 as a candidate agent for bacterial vaginosis prevention.
    Keywords: Defensin ; Vaginolysin ; Bacterial Vaginosis ; Biofilm
    ISSN: 0305-7453
    E-ISSN: 1460-2091
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  • 9
    Language: English
    In: Clinics in Perinatology, 2010, Vol.37(3), pp.677-688
    Description: Current strategies to prevent infection-related preterm birth and its associated neonatal morbidities have had limited success. Improved understanding of the pathogen-host interactions underlying altered colonization of the lower genital tract is necessary before significant progress can be made. The application of novel diagnostic techniques such as broad range PCR and proteomic analysis contribute to our knowledge of the diversity and abundance of microbial species invading the amniotic cavity as well as the resultant inflammatory response. Preterm infants delivered following intrauterine infection may respond differently to subsequent infectious challenges in the neonatal intensive care unit.
    Keywords: Preterm Birth ; Chorioamnionitis ; Bacterial Vaginosis ; Fetal Inflammatory Response ; Medicine
    ISSN: 0095-5108
    E-ISSN: 1557-9840
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  • 10
    Language: English
    In: PLoS ONE, 01 January 2015, Vol.10(3), p.e0119823
    Description: The contribution of specific factors to bacterial virulence is generally investigated through creation of genetic "knockouts" that are then compared to wild-type strains or complemented mutants. This paradigm is useful to understand the effect of presence vs. absence of a specific gene product...
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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