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.
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.
|Shannon, B; Yi, T J; Perusini, S et al. (2017) Association of HPV infection and clearance with cervicovaginal immunology and the vaginal microbiota. Mucosal Immunol 10:1310-1319|
|Tuddenham, Susan; Ghanem, Khalil G (2017) A microbiome variable in the HIV-prevention equation. Science 356:907-908|
|Oehlers, Stefan H; Flores, Maria Vega; Hall, Christopher J et al. (2017) A whole animal chemical screen approach to identify modifiers of intestinal neutrophilic inflammation. FEBS J 284:402-413|
|Shannon, B; Gajer, P; Yi, T J et al. (2017) Distinct Effects of the Cervicovaginal Microbiota and Herpes Simplex Type 2 Infection on Female Genital Tract Immunology. J Infect Dis 215:1366-1375|
|Smith, Steven B; Ravel, Jacques (2017) The vaginal microbiota, host defence and reproductive physiology. J Physiol 595:451-463|
|McClure, Erin E; Chávez, Adela S Oliva; Shaw, Dana K et al. (2017) Engineering of obligate intracellular bacteria: progress, challenges and paradigms. Nat Rev Microbiol 15:544-558|
|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|
|Ravel, Jacques; Brotman, Rebecca M (2016) Translating the vaginal microbiome: gaps and challenges. Genome Med 8:35|
|Van Lent, Sarah; De Vos, Winnok H; Huot Creasy, Heather et al. (2016) Analysis of Polymorphic Membrane Protein Expression in Cultured Cells Identifies PmpA and PmpH of Chlamydia psittaci as Candidate Factors in Pathogenesis and Immunity to Infection. PLoS One 11:e0162392|
|Nunn, Kenetta L; Forney, Larry J (2016) Unraveling the Dynamics of the Human Vaginal Microbiome. Yale J Biol Med 89:331-337|
Showing the most recent 10 out of 42 publications