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 a autolysin-induced lysis that is regulated by the ComE and CiaR response regulators, which play a favoring or protective role, respectively. We demonstrated that the ClpL ATPase, which is highly expressed during acid exposure, is required for the acidic stress-induced lysis (ASIL). ClpL carries out a chaperone function and is also involved in proteolysis in association with the serine protease ClpP. The SsrA-SmpB system mediates peptide tagging of nascent truncated proteins, which are targeted for proteolysis via the ClpP-chaperone complex. We constructed a clpL mutant that showed a complete inhibition of ASIL, indicating that this chaperone is required to fold proteins that promote ASIL. To study the proteolysis contribution to ASIL induction, we also obtained mutants of clpP and smpB genes. When the ASIL phenotype was analyzed, both clpP and smpB mutants did not autolyse at acidic pH. Considering these results, we hypothesized that acidic stressunfolded proteins are ssrA-tagged and degraded by ClpLP complex, facilitating the ASIL process. However, we cannot exclude the possibility that putative inhibitors of ASIL could be degraded directly by ClpLP through the recognition of ssrA-like tags present in their C-terminal regions, as described in E. Coli.