Role of ClpP and SsrA-dependent proteolysis in the acidic stress-induced lysis of Streptococcus pneumoniae

PIÑAS G, ALBARRACÍN ORIO A, CORTES P, ECHENIQUE J.

Carlos Paz-Córdoba, Argentina

Congreso; XLIV Annual Meeting Argentine Society for Biochemistry and Molecular Biology (SAIB); 2008

SAIB

In S. pneumoniae, we demonstrated that acidic stress triggers aautolysin-induced lysis that is regulated by the ComE and CiaRresponse regulators, which play a favoring or protective role,respectively. We demonstrated that the ClpL ATPase, which ishighly expressed during acid exposure, is required for the acidicstress-induced lysis (ASIL). ClpL carries out a chaperone functionand is also involved in proteolysis in association with the serineprotease ClpP. The SsrA-SmpB system mediates peptide tagging ofnascent truncated proteins, which are targeted for proteolysis viathe ClpP-chaperone complex. We constructed a clpL mutant thatshowed a complete inhibition of ASIL, indicating that thischaperone is required to fold proteins that promote ASIL. To studythe proteolysis contribution to ASIL induction, we also obtainedmutants of clpP and smpB genes. When the ASIL phenotype wasanalyzed, both clpP and smpB mutants did not autolyse at acidicpH. Considering these results, we hypothesized that acidic stressunfoldedproteins are ssrA-tagged and degraded by ClpLPcomplex, facilitating the ASIL process. However, we cannotexclude the possibility that putative inhibitors of ASIL could bedegraded directly by ClpLP through the recognition of ssrA-liketags present in their C-terminal regions, as described in E. Coli.