title: Staphylococcus aureus leukotoxin GH promotes inflammation.
abstract: BACKGROUND
  Staphylococcus aureus produces numerous molecules that facilitate survival in the host. We recently identified a novel S. aureus leukotoxin (leukotoxin GH [LukGH]) using proteomics, but its role in virulence remains unclear. Here we investigated the role of LukGH in vivo.
  
  
  METHODS
  We tested cytotoxicity of LukGH toward polymorphonuclear leukocytes (PMNs) from mice, rabbits, monkeys, and humans. LukGH was administered to mice, rabbits, and a cynomolgus monkey by subcutaneous or intradermal injection to assess cytotoxicity or host response in vivo. The effects of LukGH in vivo were compared with those of Panton-Valentine leukocidin (PVL), a well-characterized S. aureus leukotoxin. The contribution of LukGH to S. aureus infection was tested using mouse and rabbit infection models.
  
  
  RESULTS
  Susceptibility of PMNs to LukGH was similar between humans and cynomolgus monkeys, and was greater than that of rabbits, which in turn was greater than that of mice. LukGH or PVL caused skin inflammation in rabbits and a monkey, but deletion of neither lukGH nor lukGH and lukS/F-PV reduced severity of USA300 infections in rabbits or mice. Rather, some disease parameters (eg, rabbit abscess size) were increased following infection with a lukGH and lukS/F-PV deletion strain.
  
  
  CONCLUSIONS
  Our findings indicate that S. aureus leukotoxins enhance the host inflammatory response and influence the outcome of infection.
authors.affiliation: Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.
authors.forename: Natalia
authors.initials: N
authors.lastname: Malachowa
authors.forename: Scott D
authors.initials: SD
authors.lastname: Kobayashi
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Braughton
authors.forename: Adeline R
authors.initials: AR
authors.lastname: Whitney
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Parnell
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Gardner
authors.forename: Frank R
authors.initials: FR
authors.lastname: Deleo
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005098:Exotoxins / Q000008:administration & dosage / Q000633:toxicity*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced* / Q000276:immunology; D007271:Injections, Intradermal; D007279:Injections, Subcutaneous; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000276:immunology / Q000382:microbiology; D011817:Rabbits; D013203:Staphylococcal Infections / Q000473:pathology; D013211:Staphylococcus aureus / Q000472:pathogenicity*; D037521:Virulence Factors / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D005098:Exotoxins; D037521:Virulence Factors; C018579:leukotoxin