title: EssD, a Nuclease Effector of the Staphylococcus aureus ESS Pathway.
abstract: 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 persistent staphylococcal 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 knockout mutant or a variant lacking nuclease activity, essDL546P, elicited a diminished interleukin-12 (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.
  
  
  
  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 are 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 toward the establishment of MRSA disease.
authors: Department of Microbiology, University of Chicago, Chicago, Illinois, USA.
authors: Ryan Jay
authors: RJ
authors: Ohr
authors: Department of Microbiology, University of Chicago, Chicago, Illinois, USA.
authors: Mark
authors: M
authors: Anderson
authors: Department of Microbiology, University of Chicago, Chicago, Illinois, USA.
authors: Miaomiao
authors: M
authors: Shi
authors: Department of Microbiology, University of Chicago, Chicago, Illinois, USA.
authors: Olaf
authors: O
authors: Schneewind
authors: Department of Microbiology, University of Chicago, Chicago, Illinois, USA dmissiak@bsd.uchicago.edu.
authors: Dominique
authors: D
authors: Missiakas
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D003851:Deoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011817:Rabbits; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D003851:Deoxyribonucleases
keywords: DUF600; ESS secretion; EssD; IL-12; IL-12 signaling; MRSA; effector; nuclease