The microbiota associated with the human vagina exists in a mutualistic relationship with the human host and is believed to play an important role in women's reproductive health. The vaginal microbial communities constitute the first line of defense against infection by invasive non-indigenous organisms that cause disease, such as the sexually transmitted Chlamydia trachomatis. Despite their importance, surprisingly little is known about the composition and dynamics of vaginal microbial communities in health and disease. Traditional cultivation-based methods have provided a valuable but incomplete picture of the human vaginal microbiota. In this study, we will combine massively-parallel sequencing technology with the culture-independent analysis of the 16S rRNA gene sequence to survey the vaginal microbiota species composition and abundance in young adults with C. trachomatis infection and C. trachomatis-pos t /e women with pelvic inflammatory disease (PID). In addition, we will establish the dynamics of the community a subgroup of women sampled longitudinally over one year or more after treatment. In each of these women, we will use community transcriptomics to identify the suite of genes expressed by the vaginal microbial community. This combined data will afford a unique view of the vaginal microbiota dynamics during and after Chlamydial infection (i.e., a detailed picture of the metabolic pathways triggered in response to the infections (directly or indirectly)], and will further our model of Chlamydial infection and re-infection. Because of limitations in using humans as research subjects, guinea pigs are used as animal model for Chlamydial infections. Similarly, we will characterize the vaginal microbiota in healthy and C. caviae-infected female guinea pigs over time. Understand and characterizing the importance of the vaginal microbiota will contribute greatly to the development of new approaches based on rationale and scientifically sound principles to manipulate the vaginal microbiota in parallel to treatments. The genome of more than 200 C. trachomatis or C. caviae-isolated from these biological samples will be sequenced using 454 pyrosequencing. These sequences will represent an unparalleled resource that will be shared with the research community. The sequence data will be analyzed in correlation with the vaginal microbiota and the phenotypes characterized under the two projects of this consortium.

Public Health Relevance

Chlamydial infection are a major health risk to young sexually active women and can results in serious conditions such as pelvic inflammatory disease (PID) a cause of infertility in women. Studies on Chlamydial infections have focused on the pathogen itself. It is becoming increasingly evident that the microbes that inhabit the vagina play a critical protective role. We will examine how the vaginal microbiota reacts to Chlamydial infections and treatments in order to provide a new view of the infectious process.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI084044-04
Application #
8318049
Study Section
Special Emphasis Panel (ZAI1-MMT-M (M1))
Program Officer
Rogers, Elizabeth
Project Start
2009-09-21
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
4
Fiscal Year
2012
Total Cost
$2,434,979
Indirect Cost
$685,193
Name
University of Maryland Baltimore
Department
Microbiology/Immun/Virology
Type
Schools of Dentistry
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Ravel, Jacques; Brotman, Rebecca M (2016) Translating the vaginal microbiome: gaps and challenges. Genome Med 8:35
France, Michael T; Mendes-Soares, Helena; Forney, Larry J (2016) Genomic Comparisons of Lactobacillus crispatus and Lactobacillus iners Reveal Potential Ecological Drivers of Community Composition in the Vagina. Appl Environ Microbiol 82:7063-7073
Pittman, Kelly J; Glover, Luke C; Wang, Liuyang et al. (2016) The Legacy of Past Pandemics: Common Human Mutations That Protect against Infectious Disease. PLoS Pathog 12:e1005680
Robinson, Courtney K; Brotman, Rebecca M; Ravel, Jacques (2016) Intricacies of assessing the human microbiome in epidemiologic studies. Ann Epidemiol 26:311-21
Dareng, E O; Ma, B; Famooto, A O et al. (2016) Prevalent high-risk HPV infection and vaginal microbiota in Nigerian women. Epidemiol Infect 144:123-37
Nunn, Kenetta L; Forney, Larry J (2016) Unraveling the Dynamics of the Human Vaginal Microbiome. Yale J Biol Med 89:331-337
Neuendorf, Elizabeth; Gajer, Pawel; Bowlin, Anne K et al. (2015) Chlamydia caviae infection alters abundance but not composition of the guinea pig vaginal microbiota. Pathog Dis 73:
Wang, Liuyang; Oehlers, Stefan H; Espenschied, Scott T et al. (2015) CPAG: software for leveraging pleiotropy in GWAS to reveal similarity between human traits links plasma fatty acids and intestinal inflammation. Genome Biol 16:190
Breshears, Laura M; Edwards, Vonetta L; Ravel, Jacques et al. (2015) Lactobacillus crispatus inhibits growth of Gardnerella vaginalis and Neisseria gonorrhoeae on a porcine vaginal mucosa model. BMC Microbiol 15:276
Nunn, Kenetta L; Wang, Ying-Ying; Harit, Dimple et al. (2015) Enhanced Trapping of HIV-1 by Human Cervicovaginal Mucus Is Associated with Lactobacillus crispatus-Dominant Microbiota. MBio 6:e01084-15

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