title: α-Hemolysin, not Panton-Valentine leukocidin, impacts rabbit mortality from severe sepsis with methicillin-resistant Staphylococcus aureus osteomyelitis.
abstract: BACKGROUND
  Severe sepsis, combining acute osteomyelitis and lung involvement, has been described increasingly in healthy children with the spread of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA).
  
  
  METHODS
  Outcomes (mortality, hematogenous spread, lung and bone involvements) of rabbit osteomyelitis caused by CA-MRSA LAC(WT) USA300 and its Panton-Valentine leukocidin (PVL)- and α-hemolysin (Hla)-negative isogenic derivatives (LACΔpvl and LACΔhla, respectively) were compared.
  
  
  RESULTS
  Three days after inoculation (D3), all LAC(WT)- and LACΔpvl-, and 72% of LACΔhla-infected rabbits had no hematogenous spread and similar lung and bone bacterial densities. LACΔpvl and LACΔhla caused less severe histological lung lesions than LAC(WT) (P ≤ .01). Between D3 and D9, 10 (53%) LAC(WT)-, 11 (55%) LACΔpvl-, but no LACΔhla-infected rabbits (P < .005) died of severe sepsis with disseminated infection. Unlike deceased animals, most LAC(WT), LACΔpvl, and LACΔhla D14 survivors had no hematogenous spread (P < .001). LAC(WT) (88%) caused more bone abscesses than LACΔpvl (0, P = .001) or LACΔhla (30%, P = .01).
  
  
  CONCLUSIONS
  In this model, both PVL and Hla seemed to be required for early lung involvement via hematogenous spread. Hla, but not PVL, significantly impacted severe sepsis-related mortality. PVL was the predominant factor determining late-stage bone abscesses.
authors.affiliation: Département de Médecine Aigüe Spécialisée, Hôpital Universitaire Raymond-Poincaré, Assistance Publique-Hôpitaux de Paris, Garches.
authors.forename: Anne-Claude
authors.initials: AC
authors.lastname: Crémieux
authors.forename: Azzam
authors.initials: A
authors.lastname: Saleh-Mghir
authors.forename: Claire
authors.initials: C
authors.lastname: Danel
authors.forename: Florence
authors.initials: F
authors.lastname: Couzon
authors.forename: Oana
authors.initials: O
authors.lastname: Dumitrescu
authors.forename: Thomas
authors.initials: T
authors.lastname: Lilin
authors.forename: Christian
authors.initials: C
authors.lastname: Perronne
authors.forename: Jérôme
authors.initials: J
authors.lastname: Etienne
authors.forename: Gerard
authors.initials: G
authors.lastname: Lina
authors.forename: François
authors.initials: F
authors.lastname: Vandenesch
mesh_terms: D000038:Abscess / Q000382:microbiology; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism*; D005098:Exotoxins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D006460:Hemolysin Proteins / Q000235:genetics / Q000378:metabolism*; D007074:Immunoglobulin G / Q000097:blood; D007956:Leukocidins / Q000235:genetics / Q000378:metabolism*; D008171:Lung Diseases / Q000382:microbiology / Q000473:pathology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010019:Osteomyelitis / Q000382:microbiology* / Q000401:mortality / Q000473:pathology; D011817:Rabbits; D018805:Sepsis / Q000150:complications / Q000382:microbiology*; D013203:Staphylococcal Infections / Q000382:microbiology* / Q000401:mortality
chemical_list: D000907:Antibodies, Bacterial; D001427:Bacterial Toxins; D005098:Exotoxins; D006460:Hemolysin Proteins; D007074:Immunoglobulin G; D007956:Leukocidins; C078284:Panton-Valentine leukocidin; C021091:staphylococcal alpha-toxin
keywords: CA-MRSA; Panton-Valentine leukocidin; Staphylococcus aureus; osteomyelitis; rabbit model; severe sepsis; α-hemolysin