title: Identification of novel cytolytic peptides as key virulence determinants for community-associated MRSA.
abstract: Methicillin-resistant Staphylococcus aureus (MRSA) remains a major human pathogen. Traditionally, MRSA infections occurred exclusively in hospitals and were limited to immunocompromised patients or individuals with predisposing risk factors. However, recently there has been an alarming epidemic caused by community-associated (CA)-MRSA strains, which can cause severe infections that can result in necrotizing fasciitis or even death in otherwise healthy adults outside of healthcare settings. In the US, CA-MRSA is now the cause of the majority of infections that result in trips to the emergency room. It is unclear what makes CA-MRSA strains more successful in causing human disease compared with their hospital-associated counterparts. Here we describe a class of secreted staphylococcal peptides that have a remarkable ability to recruit, activate and subsequently lyse human neutrophils, thus eliminating the main cellular defense against S. aureus infection. These peptides are produced at high concentrations by standard CA-MRSA strains and contribute significantly to the strains' ability to cause disease in animal models of infection. Our study reveals a previously uncharacterized set of S. aureus virulence factors that account at least in part for the enhanced virulence of CA-MRSA.
authors.affiliation: Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, 903 South 4th Street, Hamilton, Montana 59840, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Braughton
authors.forename: Dorothee
authors.initials: D
authors.lastname: Kretschmer
authors.forename: Thanh-Huy L
authors.initials: TH
authors.lastname: Bach
authors.forename: Shu Y
authors.initials: SY
authors.lastname: Queck
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Adam D
authors.initials: AD
authors.lastname: Kennedy
authors.forename: David W
authors.initials: DW
authors.lastname: Dorward
authors.forename: Seymour J
authors.initials: SJ
authors.lastname: Klebanoff
authors.forename: Andreas
authors.initials: A
authors.lastname: Peschel
authors.forename: Frank R
authors.initials: FR
authors.lastname: DeLeo
authors.forename: Michael
authors.initials: M
authors.lastname: Otto
mesh_terms: D000818:Animals; D017714:Community-Acquired Infections / Q000209:etiology / Q000382:microbiology* / Q000473:pathology; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008712:Methicillin / Q000494:pharmacology*; D051379:Mice; D009504:Neutrophils / Q000382:microbiology; D010455:Peptides / Q000737:chemistry; D012867:Skin / Q000276:immunology; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000209:etiology / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000378:metabolism*; D014774:Virulence
chemical_list: D010455:Peptides; D008712:Methicillin