Identification of a distinctive phenotype for endocarditis-associated clonal complex 22 MRSA isolates with reduced vancomycin susceptibility

TY - JOUR

T1 - Identification of a distinctive phenotype for endocarditis-associated clonal complex 22 MRSA isolates with reduced vancomycin susceptibility

AU - Marbach, Helene

AU - Boakes, Eve

AU - Lynham, Steven

AU - Ward, Malcolm

AU - Otter, Jonathan A.

AU - Edgeworth, Jonathan D.

PY - 2017/5

Y1 - 2017/5

N2 - 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 (1.5–2mg l-1) 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 (1.5–2mg l-1) and low (≤0.5mg l-1) 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.

AB - 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 (1.5–2mg l-1) 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 (1.5–2mg l-1) and low (≤0.5mg l-1) 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.

KW - Endocarditis

KW - Galleria mellonella

KW - MRSA

KW - PSM

KW - Vancomycin

KW - Virulence

UR - http://www.scopus.com/inward/record.url?scp=85019926763&partnerID=8YFLogxK

U2 - 10.1099/jmm.0.000470

DO - 10.1099/jmm.0.000470

M3 - Article

C2 - 28504620

AN - SCOPUS:85019926763

SN - 0022-2615

VL - 66

SP - 584

EP - 591

JO - Journal of Medical Microbiology

JF - Journal of Medical Microbiology

IS - 5

M1 - 000470

ER -