title: Staphylococcus aureus SaeR/S-regulated factors reduce human neutrophil reactive oxygen species production.
abstract: Neutrophils are the first line of defense after a pathogen has breached the epithelial barriers, and unimpaired neutrophil functions are essential to clear infections. Staphylococcus aureus is a prevalent human pathogen that is able to withstand neutrophil killing, yet the mechanisms used by S. aureus to inhibit neutrophil clearance remain incompletely defined. The production of reactive oxygen species (ROS) is a vital neutrophil antimicrobial mechanism. Herein, we test the hypothesis that S. aureus uses the SaeR/S two-component gene regulatory system to produce virulence factors that reduce neutrophil ROS production. With the use of ROS probes, the temporal and overall production of neutrophil ROS was assessed during exposure to the clinically relevant S. aureus USA300 (strain LAC) and its isogenic mutant LACΔsaeR/S Our results demonstrated that SaeR/S-regulated factors do not inhibit neutrophil superoxide (O2-) production. However, subsequent neutrophil ROS production was significantly reduced during exposure to LAC compared with LACΔsaeR/S In addition, neutrophil H2O2production was reduced significantly by SaeR/S-regulated factors by a mechanism independent of catalase. Consequently, the reduction in neutrophil H2O2resulted in decreased production of the highly antimicrobial agent hypochlorous acid/hypochlorite anion (HOCl/-OCl). These findings suggest a new evasion strategy used by S. aureus to diminish a vital neutrophil antimicrobial mechanism.
authors.affiliation: Department of Microbiology and Immunology, Montana State University, Bozeman, Montana, USA.
authors.forename: Fermin E
authors.initials: FE
authors.lastname: Guerra
authors.affiliation: School of Medicine, University of Washington, Seattle, Washington, USA; and.
authors.forename: Conrad B
authors.initials: CB
authors.lastname: Addison
authors.affiliation: Medical Microbiology University Medical Center Utrecht, Utrecht,Netherlands.
authors.forename: Nienke W M
authors.initials: NW
authors.lastname: de Jong
authors.affiliation: Department of Microbiology and Immunology, Montana State University, Bozeman, Montana, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Azzolino
authors.affiliation: Department of Microbiology and Immunology, Montana State University, Bozeman, Montana, USA.
authors.forename: Kyler B
authors.initials: KB
authors.lastname: Pallister
authors.affiliation: Medical Microbiology University Medical Center Utrecht, Utrecht,Netherlands.
authors.forename: Jos A G
authors.initials: JA
authors.lastname: van Strijp
authors.affiliation: Department of Microbiology and Immunology, Montana State University, Bozeman, Montana, USA; jovanka@montana.edu.
authors.forename: Jovanka M
authors.initials: JM
authors.lastname: Voyich
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D002374:Catalase / Q000032:analysis; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood; D006997:Hypochlorous Acid / Q000097:blood; D008165:Luminol; D009504:Neutrophils / Q000378:metabolism* / Q000382:microbiology; D010587:Phagocytosis; D011494:Protein Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000097:blood*; D016897:Respiratory Burst; D013211:Staphylococcus aureus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D013481:Superoxides / Q000097:blood; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D017382:Reactive Oxygen Species; C433805:SaeR protein, Staphylococcus aureus; D014157:Transcription Factors; D013481:Superoxides; D008165:Luminol; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; D002374:Catalase; D011494:Protein Kinases; C527351:SaeS protein, Staphylococcus aureus
keywords: bacteria; host-pathogen interactions; innate immunity; two-component systems