Identification of Chlamydia trachomatis persistence mutants

RYAN BAXTER; ROBERT J. BASTIDAS; RAPHAEL H. VALDIVIA; HECTOR A. SAKA

New Orleans

Encuentro; CBRS 2015 Biennial Meeting; 2015

Chlamydia Basic Research Society

Background and Significance: Chlamydia trachomatis (CT) transitions into a reversible latent state called persistence during immune pressure by interferon-gamma (IFN ) or antimicrobial exposure. Persistence has been linked to the occurrence of recurrent and chronic infections in CT-infected individuals. The Chlamydia factors that regulate entry and exit from persistence are unknown. Objective: To identify genetic determinants involved in Chlamydia persistence. Methods: We carried out a screen using ~800 chemically mutagenized CT strains for defects in recovery from IFN - and/or penicillin-induced persistence. Lateral gene transfer is currently being used to map the mutations responsible for the persistence defects. Live-cell and electron microscopy are being used to characterize distinct morphological features observed in these mutants with altered persistence phenotypes. Results: Out of 8 persistence-deficient mutants identified, 4 harbor mutations (including truncations) in polymorphic membrane protein (PMP) genes. PMPs are a family of Chlamydia-specific autotransporter-like proteins with roles in adhesion and antigenic variation. In addition to being defective for persistence, a pmpC-null mutant forms bacterial aggregates within the inclusion. Conclusions: We have identified the first set of persistence-deficient CT mutants. The frequency of PMP variants in these mutants suggests that this Chlamydia-specific gene family may have an important role in persistence.