EssD, a nuclease effector of the Staphylococcus aureus ESS pathway [PublishAheadOfPrint]

EssD, a nuclease effector of the Staphylococcus aureus ESS pathway [PublishAheadOfPrint]:

Specialized secretion systems of bacteria evolved for selective advantage, either killing microbial competitors or implementing effector functions during parasitism. Earlier work characterized the ESAT-6 Secretion System (ESS) of Staphylococcus aureus and demonstrated its contribution to staphylococcal persistent infection of vertebrate hosts. Here we identify a novel secreted effector of the ESS pathway, EssD, that functions as a nuclease and cleaves DNA, but not RNA. EssI, a protein of the DUF600 family, binds EssD to block its nuclease activity in the staphylococcal cytoplasm. An essD knock out mutant or a variant lacking nuclease activity, essD^L546P, elicited a diminished IL-12 cytokine response following bloodstream infection of mice, suggesting that the effector function of EssD stimulates immune signaling to support the pathogenesis of S. aureus infections.

IMPORTANCE Bacterial type VII or ESAT-6 like secretion systems (ESS) may have evolved to modulate host immune responses during infection, thereby contributing to the pathogenesis of important diseases such as tuberculosis and methicillin-resistant S. aureus (MRSA) infection. The molecular mechanisms whereby type VII secretion systems achieve their goals is not fully elucidated, as secreted effectors with biochemical functions have heretofore not been identified. We show here that MRSA infection relies on the secretion of a nuclease effector that cleaves DNA and contributes to the stimulation of IL-12 signaling during infection. These results identify a biological mechanism for the contribution of the ESS pathway towards the establishment of MRSA disease.

http://ift.tt/2eg2PML