The Streptococcus pyogenes NAD(+) glycohydrolase modulates epithelial cell PARylation and HMGB1 release.

ABSTRACT: Streptococcus pyogenes uses the cytolysin streptolysin O (SLO) to translocate an enzyme, the S. pyogenes NAD(+) glycohydrolase (SPN), into the host cell cytosol. However, the function of SPN in this compartment is not known. As a complication, many S. pyogenes strains express a SPN variant lacking NAD(+) glycohydrolase (NADase) activity. Here, we show that SPN modifies several SLO- and NAD(+) -dependent host cell responses in patterns that correlate with NADase activity. SLO pore formation results in hyperactivation of the cellular enzyme poly-ADP-ribose polymerase-1 (PARP-1) and production of polymers of poly-ADP-ribose (PAR). However, while SPN NADase activity moderates PARP-1 activation and blocks accumulation of PAR, these processes continued unabated in the presence of NADase-inactive

SUBMITTER: Chandrasekaran S 

PROVIDER: S-EPMC4624300 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature