Fulltext

Early agr activation correlates with vancomycin treatment failure in multi-clonotype MRSA endovascular infections

Abdelhady, Wessam ; Chen, Liang ; Bayer, Arnold S. ; Seidl, Kati ; Yeaman, Michael R. ; Kreiswirth, Barry N. ; Xiong, Yan Q.

In: Journal of Antimicrobial Chemotherapy, 2015, vol. 70, no. 5, p. 1443-1452

Ajouter à la liste personnelle
    Titre
    • Early agr activation correlates with vancomycin treatment failure in multi-clonotype MRSA endovascular infections
    Auteur
    • Abdelhady, Wessam. Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA
    • Chen, Liang. Public Health Research Institute, NJMS-Rutgers University, Newark, NJ, USA
    • Bayer, Arnold S.. Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA
    • Seidl, Kati. University Hospital Zurich, University of Zurich, Zurich, Switzerland
    • Yeaman, Michael R.. Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA
    • Kreiswirth, Barry N.. Public Health Research Institute, NJMS-Rutgers University, Newark, NJ, USA
    • Xiong, Yan Q.. Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Journal of Antimicrobial Chemotherapy, 2015, vol. 70, no. 5, p. 1443-1452. Oxford University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:304351
    Summary
    Objectives Persistent MRSA infections are especially relevant to endovascular infections and correlate with suboptimal outcomes. However, the virulence signatures of Staphylococcus aureus that drive such persistence outcomes are not well defined. In the current study, we investigated correlations between accessory gene regulator (agr) activation and the outcome of vancomycin treatment in an experimental model of infective endocarditis (IE) due to MRSA strains with different agr and clonal complex (CC) types. Methods Twelve isolates with the four most common MRSA CC and agr types (CC5-agr II, CC8-agr I, CC30-agr III and CC45-agr I) were evaluated for heterogeneous vancomycin-intermediate S. aureus (hVISA), agr function, agrA and RNAIII transcription, agr locus sequences, virulence and response to vancomycin in the IE model. Results Early agr RNAIII activation (beginning at 2 h of growth) in parallel with strong δ-haemolysin production correlated with persistent outcomes in the IE model following vancomycin therapy. Importantly, such treatment failures occurred across the range of CC/agr types studied. In addition, these MRSA strains: (i) were vancomycin susceptible in vitro; (ii) were not hVISA or vancomycin tolerant; and (iii) did not evolve hVISA phenotypes or perturbed δ-haemolysin activity in vivo following vancomycin therapy. Moreover, agr locus sequence analyses revealed no common point mutations that correlated with either temporal RNAIII transcription or vancomycin treatment outcomes, encompassing different CC and agr types. Conclusions These data suggest that temporal agr RNAIII activation and agr functional profiles may be useful biomarkers to predict the in vivo persistence of endovascular MRSA infections despite vancomycin therapy