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Reduced susceptibility of Staphylococcus aureus to vancomycin and platelet microbicidal protein correlates with defective autolysis and loss of accessory gene regulator (agr) function.

Publication ,  Journal Article
Sakoulas, G; Eliopoulos, GM; Fowler, VG; Moellering, RC; Novick, RP; Lucindo, N; Yeaman, MR; Bayer, AS
Published in: Antimicrob Agents Chemother
July 2005

Loss of agr function, vancomycin exposure, and abnormal autolysis have been linked with both development of the GISA phenotype and low-level resistance in vitro to thrombin-induced platelet microbicidal proteins (tPMPs). We examined the potential in vitro interrelationships among these parameters in well-characterized, isogenic laboratory-derived and clinical Staphylococcus aureus isolates. The laboratory-derived S. aureus strains included RN6607 (agrII-positive parent) and RN6607V (vancomycin-passaged variant; hetero-GISA), RN9120 (RN6607 agr::tetM; agr II knockout parent), RN9120V (vancomycin-passaged variant), and RN9120-GISA (vancomycin passaged, GISA). Two serial isolates from a vancomycin-treated patient with recalcitrant, methicillin-resistant S. aureus (MRSA) endocarditis were also studied: A5937 (agrII-positive initial isolate) and A5940 (agrII-defective/hetero-GISA isolate obtained after prolonged vancomycin administration). In vitro tPMP susceptibility phenotypes were assessed after exposure of strains to either 1 or 2 mug/ml. Triton X-100- and vancomycin-induced lysis profiles were determined spectrophotometrically. For agrII-intact strain RN6607, vancomycin exposure in vitro was associated with modest increases in vancomycin MICs and reduced killing by tPMP, but no change in lysis profiles. In contrast, vancomycin exposure of agrII-negative RN9120 yielded a hetero-GISA phenotype and was associated with defects in lysis and reduced in vitro killing by tPMP. In the clinical isolates, loss of agrII function during prolonged vancomycin therapy was accompanied by emergence of the hetero-GISA phenotype and reduced tPMP killing, with no significant change in lysis profiles. An association was identified between loss of agrII function and the emergence of hetero-GISA phenotype during either in vitro or in vivo vancomycin exposure. In vitro, these events were associated with defective lysis and reduced susceptibility to tPMP. The precise mechanism(s) underlying these findings is the subject of current investigations.

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Published In

Antimicrob Agents Chemother

DOI

ISSN

0066-4804

Publication Date

July 2005

Volume

49

Issue

7

Start / End Page

2687 / 2692

Location

United States

Related Subject Headings

  • Vancomycin Resistance
  • Vancomycin
  • Trans-Activators
  • Staphylococcus aureus
  • Microbiology
  • Microbial Sensitivity Tests
  • Humans
  • Blood Proteins
  • Bacteriolysis
  • Bacterial Proteins
 

Citation

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Sakoulas, G., Eliopoulos, G. M., Fowler, V. G., Moellering, R. C., Novick, R. P., Lucindo, N., … Bayer, A. S. (2005). 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, 49(7), 2687–2692. https://doi.org/10.1128/AAC.49.7.2687-2692.2005
Sakoulas, George, George M. Eliopoulos, Vance G. Fowler, Robert C. Moellering, Richard P. Novick, Natalie Lucindo, Michael R. Yeaman, and Arnold S. Bayer. “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 49, no. 7 (July 2005): 2687–92. https://doi.org/10.1128/AAC.49.7.2687-2692.2005.
Sakoulas G, Eliopoulos GM, Fowler VG, Moellering RC, Novick RP, Lucindo N, 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 Jul;49(7):2687–92.
Sakoulas, George, 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, vol. 49, no. 7, July 2005, pp. 2687–92. Pubmed, doi:10.1128/AAC.49.7.2687-2692.2005.
Sakoulas G, Eliopoulos GM, Fowler VG, Moellering RC, Novick RP, Lucindo N, Yeaman MR, Bayer AS. 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 Jul;49(7):2687–2692.

Published In

Antimicrob Agents Chemother

DOI

ISSN

0066-4804

Publication Date

July 2005

Volume

49

Issue

7

Start / End Page

2687 / 2692

Location

United States

Related Subject Headings

  • Vancomycin Resistance
  • Vancomycin
  • Trans-Activators
  • Staphylococcus aureus
  • Microbiology
  • Microbial Sensitivity Tests
  • Humans
  • Blood Proteins
  • Bacteriolysis
  • Bacterial Proteins