Robert Qi1, Hwang-Soo Joo2, Batu Sharma-Kuinkel1, Nicholas R Berlon1, Lawrence Park1, Chih-Lung Fu2, Julia A Messina3, Joshua T Thaden1, Qin Yan1, Felicia Ruffin1, Stacey Maskarinec1, Bobby Warren1, Vivian H Chu1, Claudio Q Fortes4, Efthymia Giannitsioti5, Emanuele Durante-Mangoni6, Zeina A Kanafani7, Michael Otto2, Vance G Fowler8. 1. Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, NC, USA. 2. Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. 3. 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. 4. Hospital Universitario Clementino Fraga Filho/UFRJ, Rio de Janeiro, Brazil. 5. Attikon University General Hospital, Athens, Greece. 6. Internal Medicine Section, Department of Cardiothoracic Sciences, and Division of Infectious and Transplant Medicine, Second University of Naples at Monaldi Hospital, Napoli, Italy. 7. Division of Infectious Diseases, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon. 8. 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.
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. CONCLUSION: 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.
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. CONCLUSION: 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.
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