The overarching objective of project EPCRTI is the discovery of the essential correlates of chlamydial infection of the human reproductive tract in the human reproductive tract. Although not a translational project per se, project EPCRTI is conceived to prime effective translational research through two related objectives: A. the identification and characterization of chlamydial antigens of relevance to vaccine development in the naturally infected host; and B. the characterization of chlamydial metabolic, physiologic or pathogenic mechanisms that are at play in the complex, natural environment of the female genital tract and will provide targets for possible chemotherapeutic intervention. Complementary to these objectives, project EPCRTI provides an evaluation of the possible emergence of chlamydial antibiotic resistance in a well-defined patient population, of the metabolic fitness of chlamydiae in the face of host defenses and intervention, and of the resilience of the local microbiota when faced with chlamydial infection. Characterization in molecular and cellular details of the pathogen and host attributes in the site of infection is indeed essential to and must precede the future development of a safe Chlamydia vaccine and safe anti-chlamydial therapeutics.
To achieve these objectives, project EPCRTI is leveraging some of the most advanced and innovative methodologies in the study of bacterial infectious diseases. These include the definition of the vaginal microbiota using high-throughput 16S rRNA sequencing, metagenomics and metatranscriptomics to identify responses of the vaginal microbiota to chlamydial infection, the isolation of isogenic antibiotic-resistant mutants (a landmark advance in Chlamydia research) and the predictive power of biomathematical modeling of chlamydial infection and disease. The composition of the genital microbiota, the occurrence of secondary infection, the application of antibiotic treatment and the diversity of Chlamydia's physiologic attributes and genome sequence are among the common variables that are being evaluated both longitudinally and cross-sectionally, in humans and in a parallel model of chlamydial infection in the reproductive tract of the guinea pig, and on an experimental scale never attempted before.
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.
- Fierce competition between Toxoplasma and Chlamydia for host cell structures in dually infected cells.
- Effect of inflammatory response on in vivo competition between two chlamydial variants in the guinea pig model of inclusion conjunctivitis
- Chlamydia trachomatis serovar L2 can utilize exogenous lipoic acid through the action of the lipoic acid ligase LplA1
- Caring about trees in the forest: incorporating frailty in risk analysis for personalized medicine