Genetic determinants involved in the susceptibility of Pseudomonas aeruginosa to {beta}-lactam antibiotics

Antimicrobial Agents and Chemotherapy

Alvarez-Ortega C, Wiegand I, Olivares J, Hancock RE & Martínez JL.

The resistome of P. aeruginosa for three beta-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 a reduced susceptibility phenotype and 37 a supersusceptibility (i.e. altered intrinsic resistance) phenotype, with six mutants demonstrating a mixed phenotype depending on the antibiotic. Only three mutants demonstrated reduced (PA0908) or increased (glnK, 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 analyses indicated important roles for novel and known beta-lactamase regulatory genes, for genes with likely involvement in barrier function and for a range of regulators of alginate biosynthesis.