Comparative genome sequencing of an isogenic pair of USA800 clinical methicillin-resistant Staphylococcus aureus isolates obtained before and after daptomycin treatment failure

Susan Boyle-Vavra, Marcus Jones, Brett L. Gourley, Michael Holmes, Rebecca Ruf, Ashley R. Balsam, David R. Boulware, Susan Kline, Selina Jawahir, Aaron DeVries, Scott N. Peterson, Robert S. Daum

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

We describe here a clinical daptomycin treatment failure in a patient with recurrent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia in whom daptomycin was administered after a failed empirical treatment course with vancomycin and piperacillin-tazobactam. We had the opportunity to compare the genome sequences of an isogenic pair of daptomycin-susceptible and -resistant MRSA isolates obtained before and after initiation of daptomycin therapy, respectively. The genotype of both solates was USA800, ST5, SCCmec type IV, agr type II. There was no increase in cell wall thickness in the daptomycin-resistant strain despite having decreased susceptibility to both vancomycin and daptomycin. By comparing the genome sequences by pyrosequencing, we identified a polymorphism (S337L) in the tenth transmembrane segment of the multiple peptide resistance factor, MprF, encoding lysyl phosphatidylglycerol transferase. This enzyme has been shown previously to promote repulsion of daptomycin at the cell surface by addition of positively charged lysine to phosphatidylglycerol. Also, the hlb open reading frame (ORF) encoding the β-toxin was interrupted by a prophage in the daptomycin-susceptible strain; this phage was missing in the daptomycin-resistant isolate and the hlb ORF was restored. Loss of the phage in the resistant isolate also resulted in loss of the virulence factor genes clpP, scn, and sak. This is the first study to use pyrosequencing to compare the genomes of a daptomycin-susceptible/resistant MRSA isolate pair obtained during failed daptomycin therapy in humans.

Original languageEnglish (US)
Pages (from-to)2018-2025
Number of pages8
JournalAntimicrobial agents and chemotherapy
Volume55
Issue number5
DOIs
StatePublished - May 2011

Fingerprint Dive into the research topics of 'Comparative genome sequencing of an isogenic pair of USA800 clinical methicillin-resistant Staphylococcus aureus isolates obtained before and after daptomycin treatment failure'. Together they form a unique fingerprint.

  • Cite this