Mechanisms of resistance to beta-lactam antibiotics in Acinetobacter calcoaceticus

Examination of 12 strains of Acinetobacter calcoaceticus revealed that the strains expressed different constitutive levels of beta-lactamase. Mutants resistant to cefoxitin, cefoperazone or ceftazidime were selected from a strain producing a low level of beta-lactamase. All the mutants showed no change in expression of beta-lactamase, but produced penicillin-binding proteins with altered expression and/or affinity for beta-lactams. In addition, the outer membrane of the mutants showed decreased permeability (40-80% that of the parent strain) towards small hydrophilic solutes, together with diminished production of a 46.5 kDa porin protein. It was concluded that the enhanced resistance to beta-lactams in the A. calcoaceticus mutants was the result of interplay between the altered penicillin binding proteins and the reduced outer membrane permeability.