title: Increased in vitro phenol-soluble modulin production is associated with soft tissue infection source in clinical isolates of methicillin-susceptible Staphylococcus aureus.
abstract: BACKGROUND
  Phenol-soluble modulins (PSM) are amphipathic proteins produced by Staphylococcus aureus that promote virulence, inflammatory response, and biofilm formation. We previously showed that MRSA isolates from soft tissue infection (SSTI) produced significantly higher levels of PSM than MRSA isolates from hospital-acquired pneumonia (HAP) or infective endocarditis (IE). In this investigation, we sought to validate this finding in methicillin-susceptible S. aureus (MSSA) isolates.
  
  
  METHODS
  MSSA isolates (n = 162) from patients with SSTI, HAP, and IE were matched 1:1:1 based on geographic origin of the infection to form 54 triplets (North America n = 27, Europe n = 25, Australia n = 2). All isolates underwent spa typing and were classified using eGenomics. In vitro PSM production was quantified by high-performance liquid chromatography/mass spectrometry. Fischer's Exact Test and the Kruskal-Wallis test were used for statistical analysis.
  
  
  RESULTS
  Spa1 was more common in SSTI (14.81% SSTI, 3.70% HAP, 1.85% IE) (p < 0.03). Spa2 was more common in HAP (0% SSTI, 12.96% HAP, 3.70% IE) (p < 0.01). Levels of PSMα1-4 all differed significantly among the three clinical groups, with SSTI isolates producing the highest levels and IE producing the lowest levels of PSMα1-4. Spa1 isolates produced significantly more delta-toxin (p < 0.03) than non-Spa1 isolates. No associations between PSM levels and clinical outcome of SSTI, HAP, or IE were identified.
  
  
  CONCLUSIONS
  Production of PSMα1-4 is highest in SSTI MSSA isolates, supporting the hypothesis that these peptides are important for SSTI pathogenesis. These findings are similar to those described in MRSA, and demonstrate that associations between PSM levels and type of infection are independent of the methicillin-resistance status of the isolate.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Qi
authors.affiliation: Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Hwang-Soo
authors.initials: HS
authors.lastname: Joo
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: Batu
authors.initials: B
authors.lastname: Sharma-Kuinkel
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Berlon
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Park
authors.affiliation: Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Chih-Lung
authors.initials: CL
authors.lastname: Fu
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, NC, USA; Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Messina
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Thaden
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yan
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: Felicia
authors.initials: F
authors.lastname: Ruffin
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: Stacey
authors.initials: S
authors.lastname: Maskarinec
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: Bobby
authors.initials: B
authors.lastname: Warren
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: Vivian H
authors.initials: VH
authors.lastname: Chu
authors.affiliation: Hospital Universitario Clementino Fraga Filho/UFRJ, Rio de Janeiro, Brazil.
authors.forename: Claudio Q
authors.initials: CQ
authors.lastname: Fortes
authors.affiliation: Attikon University General Hospital, Athens, Greece.
authors.forename: Efthymia
authors.initials: E
authors.lastname: Giannitsioti
authors.affiliation: Internal Medicine Section, Department of Cardiothoracic Sciences, and Division of Infectious and Transplant Medicine, Second University of Naples at Monaldi Hospital, Napoli, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Durante-Mangoni
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
authors.forename: Zeina A
authors.initials: ZA
authors.lastname: Kanafani
authors.affiliation: Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Otto
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, NC, USA; Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA. Electronic address: fowle003@mc.duke.edu.
authors.forename: Vance G
authors.initials: VG
authors.lastname: Fowler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001315:Australia; D001427:Bacterial Toxins / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D005060:Europe; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D058889:Molecular Typing; D009656:North America; D018461:Soft Tissue Infections / Q000382:microbiology*; D013203:Staphylococcal Infections / Q000382:microbiology*; D013205:Staphylococcal Protein A / Q000235:genetics; D013211:Staphylococcus aureus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism*; D055815:Young Adult
chemical_list: D001427:Bacterial Toxins; D013205:Staphylococcal Protein A; C025971:staphylococcal delta toxin
keywords: Endocarditis; Methicillin-susceptible Staphylococcus aureus; Phenol-soluble modulin; Pneumonia; Skin and soft tissue infection