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1

Article

DNase inhibits Gardnerella vaginalis biofilms in vitro and in vivo (2013)

Hymes, Saul R ; Randis, Tara M ; Sun, Thomas Yang ; [et al.]

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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

DOI: 10.1093/infdis/jit047

URL: View this record in MEDLINE/PubMed

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2

Article

The Stringent Response and Arginine Metabolism Play Key Roles in Streptococcus Agalactiae Toxin Expression (2016)

Hooven, Thomas A. ; Randis, Tara M. ; Tettelin, Hervé ; [et al.]

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Language: English

In: Pediatrics, 02/2016, Vol.137(Supplement 3), pp.505A-505A

ISSN: 0031-4005

E-ISSN: 1098-4275

DOI: 10.1542/peds.137.Supplement_3.505A

Source: CrossRef

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3

Article

Inerolysin, a Cholesterol-Dependent Cytolysin Produced by Lactobacillus iners (2011)

Rampersaud, Ryan ; Planet, Paul J. ; Randis, Tara M. ; [et al.]

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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

DOI: 10.1128/JB.00694-10

URL: View this record in ASM

URL: View full text in ASM (subscribers only)

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4

Article

Pregnancy-specific association of vitamin D deficiency and bacterial vaginosis (2011)

Hensel, Katherine J ; Randis, Tara M ; Gelber, Shari E ; [et al.]

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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

DOI: 10.1016/j.ajog.2010.08.013

URL: View record in ScienceDirect (Access to full text may be restricted)

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5

Article

16: Abnormal brain imaging in infants exposed to chorioamnionitis and sepsis (2016)

Haar, Emilie Vander ; Gyamfi-Bannerman, Cynthia ; Randis, Tara M

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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

DOI: 10.1016/j.ajog.2015.10.038

URL: View record in ScienceDirect (Access to full text may be restricted)

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6

Article

Group B Streptococcus and the Vaginal Microbiota (2017)

Rosen, Geoffrey H ; Randis, Tara M ; Desai, Purnahamsi V ; [et al.]

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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

DOI: 10.1093/infdis/jix395

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7

Article

β-Hemolysin/cytolysin of Group B Streptococcus enhances host inflammation but is dispensable for establishment of urinary tract infection (2013)

Ritwij Kulkarni ; Tara M Randis ; Swati Antala ; [et al.]

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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

DOI: 10.1371/journal.pone.0059091

URL: View full text in DOAJ

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8

Article

Retrocyclin inhibits biofilm formation and toxin activity (2012)

Hooven, Thomas A. ; Randis, Tara M. ; Hymes, Saul R. ; [et al.]

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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

DOI: 10.1093/jac/dks305

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9

Article

Progress Toward Improved Understanding of Infection-Related Preterm Birth (2010)

Randis, Tara M

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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

DOI: 10.1016/j.clp.2010.06.001

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10

Article

Rational manipulation of mRNA folding free energy allows rheostat control of pneumolysin production by Streptococcus pneumoniae (2015)

Fábio E Amaral ; Dane Parker ; Tara M Randis ; [et al.]

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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

DOI: 10.1371/journal.pone.0119823

URL: View full text in DOAJ

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Berlin Brandenburg