title: EssE Promotes Staphylococcus aureus ESS-Dependent Protein Secretion To Modify Host Immune Responses during Infection.
abstract: Staphylococcus aureus, an invasive pathogen of humans and animals, requires a specialized ESS pathway to secrete proteins (EsxA, EsxB, EsxC, and EsxD) during infection. Expression of ess genes is required for S. aureus establishment of persistent abscess lesions following bloodstream infection; however, the mechanisms whereby effectors of the ESS pathway implement their virulence strategies were heretofore not known. Here, we show that EssE forms a complex with other members of the ESS secretion pathway and its substrates, promoting the secretion of EsxA, EsxB, EsxC, EsxD, and EssD. During bloodstream infection of mice, the S. aureus essE mutant displays defects in host cytokine responses, specifically in the production of interleukin-12 (IL-12) (p40/p70) and the suppression of RANTES (CCL5), activators of TH1 T cell responses and immune cell chemotaxis, respectively. Thus, essE-mediated secretion of protein effectors via the ESS pathway may enable S. aureus to manipulate host immune responses by modifying the production of cytokines.
  
  
  
  Staphylococcus aureus and other firmicutes evolved a specialized ESS (EsxA/ESAT-6-like secretion system) pathway for the secretion of small subsets of proteins lacking canonical signal peptides. The molecular mechanisms for ESS-dependent secretion and their functional purpose are still unknown. We demonstrate here that S. aureus EssE functions as a membrane assembly platform for elements of the secretion machinery and their substrates. Furthermore, S. aureus EssE-mediated secretion contributes to the production or the suppression of specific cytokines during host infection, thereby modifying immune responses toward this pathogen.
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: Ryan Jay
authors: RJ
authors: Ohr
authors: Department of Microbiology, University of Chicago, Chicago, Illinois, USA.
authors: Khaled A
authors: KA
authors: Aly
authors: Department of Microbiology, University of Chicago, Chicago, Illinois, USA.
authors: Salvatore
authors: S
authors: Nocadello
authors: Department of Microbiology, University of Chicago, Chicago, Illinois, USA.
authors: Hwan K
authors: HK
authors: Kim
authors: Department of Microbiology, University of Chicago, Chicago, Illinois, USA.
authors: Chloe E
authors: CE
authors: Schneewind
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: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002846:Chromatography, Affinity; D005260:Female; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013203:Staphylococcal Infections / Q000276:immunology / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins
keywords: ESS secretion; EssE; IL-12; MRSA; RANTES; effector