title: Clinical MRSA isolates from skin and soft tissue infections show increased in vitro production of phenol soluble modulins.
abstract: BACKGROUND
  Phenol-soluble modulins (PSMs) are amphipathic, pro-inflammatory proteins secreted by most Staphylococcus aureus isolates. This study tested the hypothesis that in vitro PSM production levels are associated with specific clinical phenotypes.
  
  
  METHODS
  177 methicillin-resistant S. aureus (MRSA) isolates from infective endocarditis (IE), skin and soft tissue infection (SSTI), and hospital-acquired/ventilator-associated pneumonia (HAP) were matched by geographic origin, then genotyped using spa-typing. In vitro PSM production was measured by high performance liquid chromatography/mass spectrometry. Statistical analysis was performed using Chi-squared or Kruskal-Wallis tests as appropriate.
  
  
  RESULTS
  Spa type 1 was significantly more common in SSTI isolates (62.7% SSTI; 1.7% IE; 16.9% HAP; p < 0.0001) while HAP and IE isolates were more commonly spa type 2 (0% SSTI; 37.3% IE; 40.7% HAP; p < 0.0001). USA300 isolates produced the highest levels of PSMs in vitro. SSTI isolates produced significantly higher quantities of PSMα1-4, PSMβ1, and δ-toxin than other isolates (p < 0.001). These findings persisted when USA300 isolates were excluded from analysis.
  
  
  CONCLUSIONS
  Increased in vitro production of PSMs is associated with an SSTI clinical source. This significant association persisted after exclusion of USA300 genotype isolates from analysis, suggesting that PSMs play a particularly important role in the pathogenesis of SSTI as compared to other infection types.
authors.affiliation: Duke U Med Center, NC, USA.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Berlon
authors.affiliation: Duke U Med Center, NC, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Qi
authors.affiliation: Duke U Med Center, NC, USA.
authors.forename: Batu K
authors.initials: BK
authors.lastname: Sharma-Kuinkel
authors.affiliation: National Institutes of Health, MD, USA.
authors.forename: Hwang-Soo
authors.initials: HS
authors.lastname: Joo
authors.affiliation: Duke U Med Center, NC, USA.
authors.forename: Lawrence P
authors.initials: LP
authors.lastname: Park
authors.affiliation: Duke U Med Center, NC, USA.
authors.forename: Dennis
authors.initials: D
authors.lastname: George
authors.affiliation: Duke U Med Center, NC, USA.
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Thaden
authors.affiliation: Duke U Med Center, NC, USA.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Messina
authors.affiliation: Duke U Med Center, NC, USA.
authors.forename: Stacey A
authors.initials: SA
authors.lastname: Maskarinec
authors.affiliation: University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Manica
authors.initials: M
authors.lastname: Mueller-Premru
authors.affiliation: Barwon Health, Deakin University, VIC, Australia.
authors.forename: Eugene
authors.initials: E
authors.lastname: Athan
authors.affiliation: Pontchaillou University, Pontchaillou, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Tattevin
authors.affiliation: Hospital Clinic - IDIBAPS. Univ. Barcelona, Spain.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Pericas
authors.affiliation: Duke U Med Center, NC, USA.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Woods
authors.affiliation: National Institutes of Health, MD, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Otto
authors.affiliation: Duke U Med Center, NC, USA. Electronic address: fowle003@mc.duke.edu.
authors.forename: Vance G
authors.initials: VG
authors.lastname: Fowler
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001427:Bacterial Toxins / Q000096:biosynthesis* / Q000737:chemistry; D017714:Community-Acquired Infections / Q000382:microbiology; D004697:Endocarditis, Bacterial / Q000382:microbiology; D005838:Genotype; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification* / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D010636:Phenols; D010641:Phenotype; D053717:Pneumonia, Ventilator-Associated / Q000382:microbiology; D012867:Skin / Q000382:microbiology*; D018461:Soft Tissue Infections / Q000382:microbiology*; D013207:Staphylococcal Skin Infections / Q000378:metabolism / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D010636:Phenols; C025971:staphylococcal delta toxin
keywords: Endocarditis; MRSA; Phenol soluble modulin; Pneumonia; Skin and soft tissue infection