Genetic determinants involved in the susceptibility of Pseudomonas aeruginosa to beta-lactam antibiotics.
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.
Alvarez-Ortega
Carolina
C
Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, CSIC, Darwin 3, Cantoblanco, Madrid, Spain.
Wiegand
Irith
I
Olivares
Jorge
J
Hancock
Robert E W
RE
Martínez
José Luis
JL
D001426:Bacterial Proteins / Q000235:genetics; D005816:Genetic Complementation Test; D008826:Microbial Sensitivity Tests; D009154:Mutation; D010641:Phenotype; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics*; D012697:Serine Endopeptidases / Q000235:genetics; D012808:Sigma Factor / Q000235:genetics; D001618:beta-Lactamases / Q000235:genetics; D047090:beta-Lactams / Q000494:pharmacology*
C079619:AlgU protein, Pseudomonas aeruginosa; D001426:Bacterial Proteins; D012808:Sigma Factor; D047090:beta-Lactams; C097649:MucD protein, Pseudomonas aeruginosa; D012697:Serine Endopeptidases; D001618:beta-Lactamases