Mutations in crrAB genes encoding a two-component regulator involved in modifications of lipopolysaccharide were searched for among a collection of colistin-resistant Klebsiella pneumoniae isolates. Four isolates, respectively, producing carbapen-emases NDM-1, OXA-181, or KPC-2 showed mutated CrrB proteins compared with those in wild-type strains. Complementation assays with a wild-type CrrB protein restored the susceptibility to colistin in all cases, confirming the involvement of the identified substitutions in the resistance phenotype.

Please use Adobe Acrobat Reader to read this book chapter for free. Just open this same document with Adobe Reader. If you do not have it, you can download it here. You can freely access the chapter at the Web Viewer here. Four general mechanisms leading to acquired antibiotic resistance have been described: (1) decreased entrance of the antibiotic into the bacterial cell; (2) increased extrusion of the antibiotic by bacterial efflux systems; (3) mutational modification of the antibiotic's target and; (4) production of antibiotic-inactivating enzymes. Characteristic examples for each mechanism are presented in Table 1. Mechanism Examples Decreased permeability Diminished expression or loss of the OprD porin in Pseudomonas aeruginosa and OmpK35, OmpK36 porins in Klebsiella pneumoniae [6-9] Efflux Overexpression of MexAB-OprM and MexXY-OprM in Pseudomonas aeruginosa and OqxAB in Klebsiella pneumoniae [10-13] Target modification Mutations of gyrases and topoisomerases leading to fluoroquinolone resistance [14-16] Inactivating enzymes Production of beta-lactamases and aminoglycoside modifying enzymes [17-19]