Bacterial vaginosis (BV) is the most common vaginal disorder among reproductive age women. BV increases a woman's risk of acquiring sexually transmitted diseases, including HIV, as well as developing infertility and pelvic inflammatory disease. In pregnant women, BV increases the risk of pre-term birth and second- and third-trimester abortion. Additionally, neonates born to mothers with BV have elevated risks of critically low birth weights, hyper-inflammatory responses, long-term developmental problems, and mortality. Given the clinical relevance of this disease, it is important to bridge gaps in the currently incomplete understanding of BV onset and progression. BV symptoms are almost always observed alongside a dramatic change in the composition of vaginal tract bacteria. Another commonly observed change is an increase in vaginal pH (normal <4.5 vs. BV>4.5). These two observations may be causally related because low pH provides a physical barrier to pathogens and other bacterial species that are either not normally found, or are at low abundances, in the healthy vaginal tract. The authors recently identified and published a tripartite association between BV, increased levels of two polyamines (putrescine and cadaverine), and several bacterial genera, including Dialister, Prevotella, and Streptococcus. Amino-acid decarboxylation and polyamine production is a well-known bacterial acid resistance and mitigation mechanism and we hypothesize it is responsible for increasing vaginal pH during BV development. Amino acid decarboxylation consumes intracellular hydrogen ions to form polyamines that are actively pumped outside the cell via amino acid/polyamine (AAP)-specific antiporters. AAP-based acid resistance has yet to be characterized among the vaginal microbiota. This project therefore proposes to address the above hypothesis by metagenomically determining the abundance and breadth of unique amino-acid decarboxylation pathways in the vaginal tract and identifying the microbial species encoding them;metatranscriptomically determining their transcriptional activity before, during and after BV;and finally by isolating important vaginal strains and precisely characterizing the in vitro conditions that lead to AAP pathway utilization.

Public Health Relevance

Bacterial vaginosis (BV) is the most common vaginal disorder among reproductive age women and is associated with increased risks of acquiring sexually transmitted diseases, infertility, gestational abortion, pre-term birth, and perinatal mortality. A hallmark of BV is increased vaginal pH and a dysbiotic microbiota. This project will fill knowledge gaps in the mechanism underlying onset and progression of BV by i) determining the abundance and breadth of unique amino-acid decarboxylation pathways in the vaginal tract and identifying the microbial species encoding them and ii) determining the ability of these pathways to mitigate vaginal acidity and the regulatory mechanisms governing their activity using in vitro culture assays.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI111145-01
Application #
8683865
Study Section
Special Emphasis Panel (ZRG1-IDM-B (80))
Program Officer
David, Hagit S
Project Start
2014-02-05
Project End
2016-01-31
Budget Start
2014-02-05
Budget End
2015-01-31
Support Year
1
Fiscal Year
2014
Total Cost
$194,400
Indirect Cost
$59,400
Name
Montana State University - Bozeman
Department
Veterinary Sciences
Type
Schools of Earth Sciences/Natur
DUNS #
625447982
City
Bozeman
State
MT
Country
United States
Zip Code
59717