Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Oct;71(4):447-57.
doi: 10.1016/j.jinf.2015.06.005. Epub 2015 Jun 14.

Clinical MRSA isolates from skin and soft tissue infections show increased in vitro production of phenol soluble modulins

Nicholas R Berlon  1 , Robert Qi  1 , Batu K Sharma-Kuinkel  1 , Hwang-Soo Joo  2 , Lawrence P Park  1 , Dennis George  1 , Joshua T Thaden  1 , Julia A Messina  1 , Stacey A Maskarinec  1 , Manica Mueller-Premru  3 , Eugene Athan  4 , Pierre Tattevin  5 , Juan M Pericas  6 , Christopher W Woods  1 , Michael Otto  2 , Vance G Fowler Jr  7
Affiliations

Clinical MRSA isolates from skin and soft tissue infections show increased in vitro production of phenol soluble modulins

Nicholas R Berlon et al. J Infect. 2015 Oct.

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.

Keywords: Endocarditis; MRSA; Phenol soluble modulin; Pneumonia; Skin and soft tissue infection.

PubMed Disclaimer

Conflict of interest statement

Conflicts of interest

Mr. Berlon reports grants from IDSA Medical Scholars Program, grants from Duke Travel Grant, during the conduct of the study. Dr. Woods reports other from bio-Merieux, non-financial support and other from Becton Dickinson, grants from Novartis, outside the submitted work. Dr. Otto reports grants from NIAID, during the conduct of the study; in addition, Dr. Otto has a patent 8,211,445 issued. Dr. Fowler reports grants from National Institutes of Health (K24-AI093969 and R01-AI068804), during the conduct of the study; personal fees from Board Membership Merck, personal fees from Consultancy from Pfizer, Novartis, Galderma, Novadigm, Durata, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co., Cerexa, Tetraphase, Trius, MedImmune, Bayer, Theravance, Cubist, Basilea, Affinergy; personal fees from Duke University Medical Center, grants from Institutional Grants/grants pending NIH, MedImmune, Forest/Cerexa, Pfizer, Merck, Advanced Liquid Logics, Theravance, Novartis, and Cubist, personal fees from Royalties (UpTo-Date), personal fees from Payment for development of educational presentations (Green Cross, Cubist, Cerexa, Durata, Theravance), outside the submitted work; In addition, Dr. Fowler has a patent NCGR pending.

Figures

Figure 1
Figure 1
Spa Type Distribution Among MRSA Isolates from Skin/Soft Tissue Infection (SSTI), Infective Endocarditis (IE), and Hospital Acquired Pneumonia (HAP). 177 MRSA isolates from SSTI, IE, and HAP underwent spa typing, with the most common 5 spa types overall plotted above (n = 125; 71% of cohort). Using Chi-squared analysis, there is a significant difference in spa type distribution among clinical groups, with isolates from SSTI being significantly more likely to be spa type 1 (Ridom t008) and significantly less likely to be spa type 2 (Ridom t002; p < 0.0001).
Figure 2
Figure 2
Mean Levels of In Vitro Phenol Soluble Modulin Production According to Infection Type of the Source MRSA Isolates. Production of PSM peptides in culture supernatant from infective endocarditis (IE), skin and soft tissue (SSTI), and hospital acquired pneumonia (HAP) isolates was quantitated and averaged over two measurements (n = 59 for each clinical group). Differences in average production between groups were calculated using separate Kruskal–Wallis tests for each peptide. Error bars correspond to the SEM. *Indicates lower production among SSTI isolates. **Indicates lower production among HAP isolates. Quantitation of all other peptides was highest among SSTI isolates.
Figure 3
Figure 3
Mean Levels of In Vitro Phenol Soluble Modulin Production among USA300 Isolates vs All Other Isolates. Average production of PSM peptides in culture supernatant from USA300 MRSA isolates (n = 44) was compared to non-USA300 MRSA isolates (n = 133). Differences in average production between groups were calculated using separate Kruskal–Wallis tests for each peptide. Error bars correspond to the SEM. *Indicates lower production among SSTI isolates. Quantitation of all other peptides was highest among SSTI isolates.
Figure 4
Figure 4
Mean Levels of In Vitro Phenol Soluble Modulin Production According to Infection Type of the Source MRSA Isolates Excluding USA300. Analysis of average PSM peptide production was repeated for each clinical group after excluding USA300 isolates (IE n = 58; SSTI n = 24; HAP n = 51). Differences in average production between groups were calculated using separate Kruskal–Wallis tests for each peptide. Error bars correspond to the SEM. *Indicates lower production among SSTI isolates. **Indicates lower production among HAP isolates.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Murdoch DR, Corey GR, Hoen B, Miro JM, Fowler VG, Jr, Bayer AS, et al. Clinical presentation, etiology, and outcome of infective endocarditis in the 21st century: the International Collaboration on Endocarditis-Prospective Cohort Study. Archives Intern Med. 2009;169(5):463–73. - PMC - PubMed
    1. Doern GV, Jones RN, Pfaller MA, Kugler KC, Beach ML. Bacterial pathogens isolated from patients with skin and soft tissue infections: frequency of occurrence and antimicrobial susceptibility patterns from the SENTRY Antimicrobial Surveillance Program (United States and Canada, 1997). SENTRY Study Group (North America) Diagnostic Microbiol Infect Dis. 1999;34(1):65–72. - PubMed
    1. Weber DJ, Rutala WA, Sickbert-Bennett EE, Samsa GP, Brown V, Niederman MS. Microbiology of ventilator-associated pneumonia compared with that of hospital-acquired pneumonia. Infect Control Hosp Epidemiol. 2007;28(7):825–31. - PubMed
    1. Periasamy S, Joo HS, Duong AC, Bach TH, Tan VY, Chatterjee SS, et al. How Staphylococcus aureus biofilms develop their characteristic structure. Proc Natl Acad Sci USA. 2012;109(4):1281–6. - PMC - PubMed
    1. Otto M. Phenol-soluble modulins. Int J Med Microbiol. 2014;304(2):164–9. - PMC - PubMed

Publication types

MeSH terms