title: Neutrophil-generated oxidative stress and protein damage in Staphylococcus aureus.
abstract: Staphylococcus aureus is a ubiquitous, versatile and dangerous pathogen. It colonizes over 30% of the human population, and is one of the leading causes of death by an infectious agent. During S. aureus colonization and invasion, leukocytes are recruited to the site of infection. To combat S. aureus, leukocytes generate an arsenal of reactive species including superoxide, hydrogen peroxide, nitric oxide and hypohalous acids that modify and inactivate cellular macromolecules, resulting in growth defects or death. When S. aureus colonization cannot be cleared by the immune system, antibiotic treatment is necessary and can be effective. Yet, this organism quickly gains resistance to each new antibiotic it encounters. Therefore, it is in the interest of human health to acquire a deeper understanding of how S. aureus evades killing by the immune system. Advances in this field will have implications for the design of future S. aureus treatments that complement and assist the host immune response. In that regard, this review focuses on how S. aureus avoids host-generated oxidative stress, and discusses the mechanisms used by S. aureus to survive oxidative damage including antioxidants, direct repair of damaged proteins, sensing oxidant stress and transcriptional changes. This review will elucidate areas for studies to identify and validate future antimicrobial targets.
authors.affiliation: Department of Pathology, Microbiology and Immunology, U.S. Department of Veteran Affairs, Vanderbilt Institute of Chemical Biology, Vanderbilt University School of Medicine, 1161 21st Avenue South, Medical Center North, Nashville, TN 37232, USA.
authors.forename: William N
authors.initials: WN
authors.lastname: Beavers
authors.affiliation: Department of Pathology, Microbiology and Immunology, U.S. Department of Veteran Affairs, Vanderbilt Institute of Chemical Biology, Vanderbilt University School of Medicine, 1161 21st Avenue South, Medical Center North, Nashville, TN 37232, USA Tennessee Valley Healthcare System, U.S. Department of Veteran Affairs, Vanderbilt Institute of Chemical Biology, Vanderbilt University School of Medicine, 1161 21st Avenue South, Nashville, TN 37232, USA eric.skaar@vanderbilt.edu.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Skaar
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D050296:Microbial Viability / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D009569:Nitric Oxide; D016877:Oxidants / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D016897:Respiratory Burst; D013203:Staphylococcal Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000502:physiology*
chemical_list: D016877:Oxidants; D009569:Nitric Oxide
keywords: Staphylococcus aureus; antioxidant defenses; host–pathogen interface; neutrophils; oxidative stress; protein oxidation