The microbiota associated with the human vagina exists in a mutualisfic relafionship with the human host and is believed to play an important role in women's reproducfive 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 litfie is known about the composition and dynamics of vaginal microbial communifies in health and disease. Traditional culfivafion-based methods have provided a valuable but incomplete picture of the human vaginal microbiota. In this study, we will combined massively-parallel sequencing technology with the culture-independent analysis of the 16S rRNA gene sequence to survey the vaginal microbiota species composifion and abundance in young adults with C. trachomatis infecfion and C. frac/70/r7af/s-positive women with pelvic inflammatory disease (PID). In addifion, 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 infecfion (i.e., a detailed picture of the metabolic pathways triggered in response to the infecfions (direcfiy or indirectly)], and will further our model of Chlamydial infecfion and re-ihfecfion. Because of limitations in using humans as research subjects, guinea pigs are used as animal model for Chlamydial infections. Similarlly, we will characterize the vaginal microbiota in healthy and C. cawae-infected female guinea pigs over time. Understand and characterizing the importance of the vaginal microbiota will contribute greafiy to the development of new approaches based on rafionale and scienfifically 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 correlafion with the vaginal microbiota and the phenotypes characterized under the two projects of this consortium.

Public Health Relevance

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

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1-MMT-M)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Maryland Baltimore
United States
Zip Code
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

Showing the most recent 10 out of 35 publications