EPSTI: Eco-Pathogenomics of Sexually Transmitted Infections

This project is a collaboration with Dr. Patrik Bavoil (co-PI) at the University of Maryland School of Dentistry.

The "Eco-Pathogenomics of Sexually Transmitted Infections" (EPSTI), project builds upon the research started under the "Eco-Pathogenomics of Chlamydial Reproductive Tract Infection"(EPCRTI) project and examines the triangular relationship between human genetic variation, sexually transmitted infections (STIs) and co-infections caused by Chlamydia trachomatis andNeisseria gonorrhoeae, and microbiota composition among partners with distinct infection outcomes. Sexually transmitted infections pose a major health challenge in the United States where Chlamydia trachomatis (CT) genital infections, with an estimated 2.8M cases yearly, are the most frequently reported bacterial infectious disease. Likewise there are an estimated 820,000 cases of Neisseria gonorrhoeae (GC) each year. The sequelae of infections and co-infections caused by these two pathogens are insidious and account for the majority of the 750,000 annual cases of pelvic inflammatory disease (PID) in the United States, a precursor to life-threatening ectopic pregnancy and tubal factor infertility (TFI) in women. Thus, research to prevent, control and treat these STIs will provide broad health and economic benefits. 

In the battleground of an infection site, both the host cells and the microbes employ complex signaling mechanisms and weaponry to destabilize, neutralize or kill the other. Identifying and understanding these biomarkers of infection and disease are the main research goals of this Cooperative Research Center (CRC). The anticipated impact will be to reduce the incidence of sexually transmitted infections and diseases (STIs & STDs) in humans worldwide. We believe that: a) the genetic variance of the infected host, the genetic diversity of the infecting pathogen(s), and the composition and function of the resident microbiota directly impact the evolution of STIs and could be biomarkers of disease severity or protection from STIs; b) genes, RNAs and proteins that are expressed or produced by the host, the pathogens, and/or the genital microbiota in response to one another are biomarkers of a specific type of STI or STD. The aim of the CRC is therefore to identify host, pathogen and/or microbiota biomarkers of STIs that may reveal mechanisms of pathogenesis and therapeutic or diagnostic targets that can be exploited for the development of translational curative or prophylactic interventions that have a direct impact in public health. 

To test these hypotheses and realize these objectives, this CRC, EPSTI, will build on data acquired by the parent CRC, EPCRTI, a Chlamydia-centric program that laid the methodological and conceptual foundations of EPSTI. Within EPSTI, STING (STI Network Groups), consisting of multiple networks of sexual partners, will be leveraged to examine the triangular relationship between human genetic variation, CT, GC infections and co-infections, and microbiota composition among partners with distinct infection outcomes. The experimental approach will adopt a systems biology strategy focused on the identification of biomarkers of genital/reproductive infection and disease and are eminently amenable to translational applications in clinical and public health. These are expected to include predictive diagnosis for individuals at greatest risk of STI and STD based on their biological and microbiome characteristics, development of sensitive and specific point-of-care diagnostic tests and highly specific targets for vaccine development. 

This Sexually Transmitted Infections Cooperative Research Center (STI CRC) is funded through grant U19 AI08044 from the National Institutes of Health, National Institute for Allergies and Infectious Disease.