1887

Abstract

Purpose. We previously identified an association between CC22 meticillin-resistant Staphylococcus aureus (MRSA) bloodstream infection isolates with an elevated vancomycin MIC (V-MIC) in the susceptible range (1.5–2 mg l) and endocarditis. This study explores whether these isolates have a specific phenotype consistent with the clinical findings.

Methodology. CC22 and CC30 MRSA isolates with high (1.5–2 mg l) and low (≤0.5 mg l) V-MICs were tested for fibrinogen and fibronectin binding, virulence in a Galleria mellonella caterpillar model, phenol soluble modulin production and accessory gene regulator (agr) expression.

Results. CC22 high V-MIC, but not CC30 high V-MIC isolates, showed sustained fibrinogen binding through a stationary growth phase and increased PSM production, specifically PSMα1, compared with respective low V-MIC isolates. Expression was lower in both CC22 and CC30 high V-MIC isolates compared with respective low V-MIC isolates, although there was no associated reduction in virulence in the caterpillar model.

Conclusions. The identification of a distinct phenotype for CC22 high V-MIC isolates supports the hypothesis that bacterial factors contribute to the mechanism underlying their association with endocarditis. Further study of these isolates could shed light on the molecular mechanism of endocarditis in humans.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.000470
2017-05-15
2019-10-18
Loading full text...

Full text loading...

/deliver/fulltext/jmm/66/5/584.html?itemId=/content/journal/jmm/10.1099/jmm.0.000470&mimeType=html&fmt=ahah

References

  1. Boucher H, Miller LG, Razonable RR. Serious infections caused by methicillin-resistant Staphylococcus aureus. Clin Infect Dis 2010;51:S183–S197 [CrossRef][PubMed]
    [Google Scholar]
  2. Miller CE, Batra R, Cooper BS, Patel AK, Klein J et al. An association between bacterial genotype combined with a high-vancomycin minimum inhibitory concentration and risk of endocarditis in methicillin-resistant Staphylococcus aureus bloodstream infection. Clin Infect Dis 2012;54:591–600 [CrossRef][PubMed]
    [Google Scholar]
  3. Xiong YQ, Fowler VG, Yeaman MR, Perdreau-Remington F, Kreiswirth BN et al. Phenotypic and genotypic characteristics of persistent methicillin-resistant Staphylococcus aureus bacteremia in vitro and in an experimental endocarditis model. J Infect Dis 2009;199:201–208 [CrossRef][PubMed]
    [Google Scholar]
  4. Nienaber JJ, Sharma Kuinkel BK, Clarke-Pearson M, Lamlertthon S, Park L et al. Methicillin-susceptible Staphylococcus aureus endocarditis isolates are associated with clonal complex 30 genotype and a distinct repertoire of enterotoxins and adhesins. J Infect Dis 2011;204:704–713 [CrossRef][PubMed]
    [Google Scholar]
  5. Nethercott C, Mabbett AN, Totsika M, Peters P, Ortiz JC et al. Molecular characterization of endocarditis-associated Staphylococcus aureus. J Clin Microbiol 2013;51:2131–2138 [CrossRef][PubMed]
    [Google Scholar]
  6. Chi CY, Wang SM, Lin CC, Liu CC. Microbiological characteristics of community-associated Staphylococcus aureus causing uncomplicated bacteremia and infective endocarditis. J Clin Microbiol 2010;48:292–294 [CrossRef][PubMed]
    [Google Scholar]
  7. Abdelhady W, Bayer AS, Seidl K, Nast CC, Kiedrowski MR et al. Reduced vancomycin susceptibility in an in vitro catheter-related biofilm model correlates with poor therapeutic outcomes in experimental endocarditis due to methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 2013;57:1447–1454 [CrossRef][PubMed]
    [Google Scholar]
  8. Holmes NE, Johnson PD, Howden BP. Relationship between vancomycin-resistant Staphylococcus aureus, vancomycin-intermediate S. aureus, high vancomycin MIC, and outcome in serious S. aureus infections. J Clin Microbiol 2012;50:2548–2552 [CrossRef][PubMed]
    [Google Scholar]
  9. Howden BP, Davies JK, Johnson PD, Stinear TP, Grayson ML. Reduced vancomycin susceptibility in Staphylococcus aureus, including vancomycin-intermediate and heterogeneous vancomycin-intermediate strains: resistance mechanisms, laboratory detection, and clinical implications. Clin Microbiol Rev 2010;23:99–139 [CrossRef][PubMed]
    [Google Scholar]
  10. Sakoulas G, Eliopoulos GM, Fowler VG, Moellering RC, Novick RP et al. Reduced susceptibility of Staphylococcus aureus to vancomycin and platelet microbicidal protein correlates with defective autolysis and loss of accessory gene regulator (agr) function. Antimicrob Agents Chemother 2005;49:2687–2692 [CrossRef][PubMed]
    [Google Scholar]
  11. Passalacqua KD, Satola SW, Crispell EK, Read TD. A mutation in the PP2C phosphatase gene in a Staphylococcus aureus USA300 clinical isolate with reduced susceptibility to vancomycin and daptomycin. Antimicrob Agents Chemother 2012;56:5212–5223 [CrossRef][PubMed]
    [Google Scholar]
  12. Renzoni A, Francois P, Li D, Kelley WL, Lew DP et al. Modulation of fibronectin adhesins and other virulence factors in a teicoplanin-resistant derivative of methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 2004;48:2958–2965 [CrossRef][PubMed]
    [Google Scholar]
  13. Peleg AY, Monga D, Pillai S, Mylonakis E, Moellering RC et al. Reduced susceptibility to vancomycin influences pathogenicity in Staphylococcus aureus infection. J Infect Dis 2009;199:532–536 [CrossRef][PubMed]
    [Google Scholar]
  14. Jacob JT, Diazgranados CA. High vancomycin minimum inhibitory concentration and clinical outcomes in adults with methicillin-resistant Staphylococcus aureus infections: a meta-analysis. Int J Infect Dis 2013;17:e93e100 [CrossRef][PubMed]
    [Google Scholar]
  15. van Hal SJ, Lodise TP, Paterson DL. The clinical significance of vancomycin minimum inhibitory concentration in Staphylococcus aureus infections: a systematic review and meta-analysis. Clin Infect Dis 2012;54:755–771 [CrossRef][PubMed]
    [Google Scholar]
  16. Christensen GD, Simpson WA, Bisno AL, Beachey EH. Adherence of slime-producing strains of Staphylococcus epidermidis to smooth surfaces. Infect Immun 1982;37:318–326[PubMed]
    [Google Scholar]
  17. Wang R, Braughton KR, Kretschmer D, Bach TH, Queck SY et al. Identification of novel cytolytic peptides as key virulence determinants for community-associated MRSA. Nat Med 2007;13:1510–1514 [CrossRef][PubMed]
    [Google Scholar]
  18. Joo HS, Cheung GY, Otto M. Antimicrobial activity of community-associated methicillin-resistant Staphylococcus aureus is caused by phenol-soluble modulin derivatives. J Biol Chem 2011;286:8933–8940 [CrossRef][PubMed]
    [Google Scholar]
  19. Anderson L, Hunter CL. Quantitative mass spectrometric multiple reaction monitoring assays for major plasma proteins. Mol Cell Proteomics 2006;5:573–588 [CrossRef][PubMed]
    [Google Scholar]
  20. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein–dye binding. Anal Biochem 1976;72:248–254 [CrossRef][PubMed]
    [Google Scholar]
  21. Joo HS, Chan JL, Cheung GY, Otto M. Subinhibitory concentrations of protein synthesis-inhibiting antibiotics promote increased expression of the agr virulence regulator and production of phenol-soluble modulin cytolysins in community-associated methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 2010;54:4942–4944 [CrossRef][PubMed]
    [Google Scholar]
  22. Yuan JS, Reed A, Chen F, Stewart CN. Statistical analysis of real-time PCR data. BMC Bioinformatics 2006;7:85 [CrossRef][PubMed]
    [Google Scholar]
  23. Piroth L, Que YA, Widmer E, Panchaud A, Piu S et al. The fibrinogen- and fibronectin-binding domains of Staphylococcus aureus fibronectin-binding protein A synergistically promote endothelial invasion and experimental endocarditis. Infect Immun 2008;76:3824–3831 [CrossRef][PubMed]
    [Google Scholar]
  24. Que YA, Haefliger JA, Piroth L, François P, Widmer E et al. Fibrinogen and fibronectin binding cooperate for valve infection and invasion in Staphylococcus aureus experimental endocarditis. J Exp Med 2005;201:1627–1635 [CrossRef][PubMed]
    [Google Scholar]
  25. Ythier M, Entenza JM, Bille J, Vandenesch F, Bes M et al. Natural variability of in vitro adherence to fibrinogen and fibronectin does not correlate with in vivo infectivity of Staphylococcus aureus. Infect Immun 2010;78:1711–1716 [CrossRef][PubMed]
    [Google Scholar]
  26. Schwartz K, Syed AK, Stephenson RE, Rickard AH, Boles BR. Functional amyloids composed of phenol soluble modulins stabilize Staphylococcus aureus biofilms. PLoS Pathog 2012;8:e1002744 [CrossRef][PubMed]
    [Google Scholar]
  27. Wang R, Khan BA, Cheung GY, Bach TH, Jameson-Lee M et al. Staphylococcus epidermidis surfactant peptides promote biofilm maturation and dissemination of biofilm-associated infection in mice. J Clin Invest 2011;121:238–248 [CrossRef][PubMed]
    [Google Scholar]
  28. Donlan RM, Costerton JW. Biofilms: survival mechanisms of clinically relevant microorganisms. Clin Microbiol Rev 2002;15:167–193 [CrossRef][PubMed]
    [Google Scholar]
  29. Laplante KL, Woodmansee S. Activities of daptomycin and vancomycin alone and in combination with rifampin and gentamicin against biofilm-forming methicillin-resistant Staphylococcus aureus isolates in an experimental model of endocarditis. Antimicrob Agents Chemother 2009;53:3880–3886 [CrossRef][PubMed]
    [Google Scholar]
  30. Voyich JM, Braughton KR, Sturdevant DE, Whitney AR, Saïd-Salim B et al. Insights into mechanisms used by Staphylococcus aureus to avoid destruction by human neutrophils. J Immunol 2005;175:3907–3919 [CrossRef][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.000470
Loading
/content/journal/jmm/10.1099/jmm.0.000470
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error