Genetic determinants involved in the susceptibility of Pseudomonas aeruginosa to β-lactam antibiotics

Carolina Alvarez-Ortega, Irith Wiegand, JORGE ANDRES OLIVARES PACHECO, Robert E.W. Hancock, José Luis Martínez

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103 Scopus citations

Abstract

The resistome of P. aeruginosa for three β-lactam antibiotics, namely, ceftazidime, imipenem, and meropenem, was deciphered by screening a comprehensive PA14 mutant library for mutants with increased or reduced susceptibility to these antimicrobials. Confirmation of the phenotypes of all selected mutants was performed by Etest. Of the total of 78 confirmed mutants, 41 demonstrated a reduced susceptibility phenotype and 37 a supersusceptibility (i.e., altered intrinsic resistance) phenotype, with 6 mutants demonstrating a mixed phenotype, depending on the antibiotic. Only three mutants demonstrated reduced (PA0908) or increased (glnK and ftsK) susceptibility to all three antibiotics. Overall, the mutant profiles of susceptibility suggested distinct mechanisms of action and resistance for the three antibiotics despite their similar structures. More detailed analysis indicated important roles for novel and known β-lactamase regulatory genes, for genes with likely involvement in barrier function, and for a range of regulators of alginate biosynthesis.

Original languageEnglish
Pages (from-to)4159-4167
Number of pages9
JournalAntimicrobial Agents and Chemotherapy
Volume54
Issue number10
DOIs
StatePublished - 1 Oct 2010

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