Structural and molecular basis of resistance to aminoglycoside antibiotics by APH(3')-IIb from Pseudomonas aeruginosa

Abstract

Pseudomonas aeruginosa is one of the six bacteria of greatest concern identified by the WHO for its resistance to antibiotics. In the case of aminoglycosides, used in combination with other antibiotics in the treatment of severe infections, resistance is mainly due to modification of the antibiotic by bacterial enzymes. In this study, we have functionally and structurally characterized one such enzyme from P. aeruginosa, aminoglycoside 3-O-phosphotransferase IIb, APH(3)-IIb. The results will provide a better understanding of this resistance mechanism and enable us to envisage solutions for blocking it and restoring the efficacy of aminoglycosides.