Disruption of CTL0175 Hampers Chlamydia trachomatis Replication Post IFNgamma-Induced Stress

PANZETTA, MARÍA E.; LUJÁN, AGUSTÍN L.; BASTIDAS, ROBERT J.; DAMIANI, MARÍA T.; VALDIVIA, RAPHAEL H.; SAKA HÉCTOR A.

Paraná

Congreso; SAIB 2018 - 54th Anual Meeting Argentine Society of Biochemistry and Molecular Biology; 2018

SAIB

Chlamydia trachomatis (CT) is the most common sexually transmitted bacterial pathogen globally. CT causes asymptomatic, persistent infections leading to serious complications, particularly in young women. CT is an obligate intracellular bacterium alternating between two developmental forms: the infectious elementary body (EB) and the non-infectious, replicative reticulate body (RB). In presence of stressors such as interferon-gamma (IFN), CT enters a viable but non-cultivable or ?persistent? state. Once the stressors are removed, CT resumes replication and continues to propagate. In a high throughput screen to identify chlamydial genes involved in persistence, we previously found that null mutations in ctl0175/ptr (encoding an uncharacterized hypothetical protease), lead to a significant decrease in the generation of infectious progeny after IFN-induced stress. In Chlamydia, this may be due to reduced genome replication or to blocked RB/EB differentiation. We generated a ptr::GII (ptr knockout) strain and quantified the rate of genome accumulation during IFN-treatment and recovery, compared to the wild type L2 strain. We found that ptr::GII exhibits reduced genome replication during recovery post IFN-induced stress, indicating that ptr is required for engaging rapid exit of persistence and replication upon IFN removal. We used a female genital tract model of infection in mice and surprisingly found increased chlamydial burden at 14 days post-infection for the ptr::GII strain. Overall, these results point that a reduced replication rate upon IFN removal enhances the ability of this bacteria to establish a long-lasting infection in the uterus.