The Resistome of Pseudomonas aeruginosa in Relationship to Phenotypic Susceptibility

  • Veronica N. Kos
    Infection Innovative Medicines Unit, AstraZeneca R&D Boston, Waltham, Massachusetts, USA
  • Maxime Déraspe
    Infectious Diseases Research Center, Laval University, Quebec, Quebec, Canada
  • Robert E. McLaughlin
    Infection Innovative Medicines Unit, AstraZeneca R&D Boston, Waltham, Massachusetts, USA
  • James D. Whiteaker
    Infection Innovative Medicines Unit, AstraZeneca R&D Boston, Waltham, Massachusetts, USA
  • Paul H. Roy
    Infectious Diseases Research Center, Laval University, Quebec, Quebec, Canada
  • Richard A. Alm
    Infection Innovative Medicines Unit, AstraZeneca R&D Boston, Waltham, Massachusetts, USA
  • Jacques Corbeil
    Infectious Diseases Research Center, Laval University, Quebec, Quebec, Canada
  • Humphrey Gardner
    Infection Innovative Medicines Unit, AstraZeneca R&D Boston, Waltham, Massachusetts, USA

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<jats:title>ABSTRACT</jats:title> <jats:p> Many clinical isolates of <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Pseudomonas aeruginosa</jats:named-content> cause infections that are difficult to eradicate due to their resistance to a wide variety of antibiotics. Key genetic determinants of resistance were identified through genome sequences of 390 clinical isolates of <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. aeruginosa</jats:named-content> , obtained from diverse geographic locations collected between 2003 and 2012 and were related to microbiological susceptibility data for meropenem, levofloxacin, and amikacin. β-Lactamases and integron cassette arrangements were enriched in the established multidrug-resistant lineages of sequence types ST111 (predominantly O12) and ST235 (O11). This study demonstrates the utility of next-generation sequencing (NGS) in defining relevant resistance elements and highlights the diversity of resistance determinants within <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. aeruginosa</jats:named-content> . This information is valuable in furthering the design of diagnostics and therapeutics for the treatment of <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. aeruginosa</jats:named-content> infections. </jats:p>

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