title: The resistome of Pseudomonas aeruginosa in relationship to phenotypic susceptibility.
abstract: Many clinical isolates of Pseudomonas aeruginosa 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 P. aeruginosa, 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 P. aeruginosa. This information is valuable in furthering the design of diagnostics and therapeutics for the treatment of P. aeruginosa infections.
authors.affiliation: Infection Innovative Medicines Unit, AstraZeneca R&D Boston, Waltham, Massachusetts, USA veronica.kos@astrazeneca.com.
authors.forename: Veronica N
authors.initials: VN
authors.lastname: Kos
authors.affiliation: Infectious Diseases Research Center, Laval University, Quebec, Quebec, Canada.
authors.forename: Maxime
authors.initials: M
authors.lastname: Déraspe
authors.affiliation: Infection Innovative Medicines Unit, AstraZeneca R&D Boston, Waltham, Massachusetts, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: McLaughlin
authors.affiliation: Infection Innovative Medicines Unit, AstraZeneca R&D Boston, Waltham, Massachusetts, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Whiteaker
authors.affiliation: Infectious Diseases Research Center, Laval University, Quebec, Quebec, Canada.
authors.forename: Paul H
authors.initials: PH
authors.lastname: Roy
authors.affiliation: Infection Innovative Medicines Unit, AstraZeneca R&D Boston, Waltham, Massachusetts, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Alm
authors.affiliation: Infectious Diseases Research Center, Laval University, Quebec, Quebec, Canada.
authors.forename: Jacques
authors.initials: J
authors.lastname: Corbeil
authors.affiliation: Infection Innovative Medicines Unit, AstraZeneca R&D Boston, Waltham, Massachusetts, USA.
authors.forename: Humphrey
authors.initials: H
authors.lastname: Gardner
mesh_terms: D000583:Amikacin / Q000494:pharmacology* / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015373:Bacterial Typing Techniques; D001483:Base Sequence; D004269:DNA, Bacterial / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D016680:Genome, Bacterial / Q000235:genetics; D006801:Humans; D064704:Levofloxacin / Q000494:pharmacology* / Q000627:therapeutic use; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D058885:Multilocus Sequence Typing; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D017422:Sequence Analysis, DNA; D013845:Thienamycins / Q000494:pharmacology* / Q000627:therapeutic use; D001618:beta-Lactamases / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D013845:Thienamycins; D064704:Levofloxacin; D000583:Amikacin; D001618:beta-Lactamases; D000077731:Meropenem