Chlamydia trachomatis Ptr is required for efficient recovery upon IFNγ-induced persistence.

LUJAN, A.; VALDIVIA, RAPHAEL H.; BASTIDAS, ROBERT J.; SAKA, HÉCTOR A.; PANZETTA, ME.; DAMIANI, MARÍA T.

Seattle

Congreso; 9th Biennial Meeting CBRS (Chlamydia Basic Research Society); 2019

CBRS Chlamydia Basic Research Society

Chlamydia trachomatis (CT) is the leading sexually transmitted bacterial pathogen and a frequent cause of asymptomatic, persistent infections leading to serious complications. Chlamydia displays an obligate intracellular lifestyle involving the infectious elementary body and the replicative reticulate body. In the presence of stressors such as gamma-interferon (IFNg) or beta-lactams, CT undergoes an interruption in its replication cycle and enters a viable but non-cultivable, ?persistent? state, usually associated with the presence of aberrant reticulate bodies. Upon removal of the stressors, CT resumes cell division and developmental transitions. We performed a genetic screen to identify CT mutants with defects in recovery upon IFNg- and/or penicillin-induced stress and characterized a chemically-mutagenized CT strain that exhibited a significant decrease in the generation of infectious progeny upon recovery from IFNg- but not penicillin-induced stress. Through lateral gene transfer and targeted insertional gene inactivation we identified ptr, encoding a putative exported protease, as a gene required for resistance to IFNg-induced stress. A ptr-null strain (ptr::GII) displayed reduced progeny generation upon IFNg-induced stress and this defect was restored by complementation of Ptr expression. Also, the ptr::GII mutant displayed reduced genome accumulation during recovery post IFNg-induced stress, suggesting that ptr is required for engaging a rapid exit from persistence. Finally, we used a murine genital tract model of infection and found impaired clearance at 14 days post-infection for ptr::GII. Overall, our findings indicate that ptr is required for rapid recovery upon IFNg-induced stress in vitro and that lack of Ptr results in impaired clearance of CT in mice.