Identification of Chlamydia trachomatis mutants defective for persistence

H. A. SAKA; RYAN BAXTER; ROBERT J. BASTIDAS; MARIA EMILIA PANZETTA; RAPHAEL VALDIVIA

Rosario

Congreso; SAIB 2014; 2014

Chlamydia trachomatis (CT) is a leading cause of genital and ocular diseases worldwide. Upon exposure to antimicrobial compounds such as interferon-gamma (IFNg) or beta-lactams, CT transitions into a latent state called persistence. In this state, CT can evade immune detection for long periods of time and transition back into an infectious form once antimicrobial compounds have been removed. Chlamydial persistence has been linked to the occurrence of recurrent and chronic infections in infected individuals. Due to a limited array of molecular genetic tools for routine genetic manipulations in Chlamydia, bacterial factors regulating chlamydial persistence remain poorly elucidated. Taking advantage of a collection of ~800 chemically mutagenized CT mutant strains, we carried out a high throughput screen and identified 8 mutants defective in recovering from IFNg- and/or penicillin-induced persistence. By whole genome sequencing, we find that 4 of these strains harbor mutations (including truncations) in genes coding for polymorphic membrane proteins (PMPs). PMPs are a family of Chlamydia¬-specific autotransporter-like proteins linked to adhesion and antigenic variation. We are currently backcrossing these mutant strains into a wild type background and utilizing recombinant strains to assess whether PMP gene products are linked to persistence.