Enhanced resistance to cefotaxime and imipenem associated with outer membrane protein alterations in Enterobacter aerogenes

Mutants exhibiting enhanced resistance to cefotaxime and imipenem were selected by plating a strain of Enterobacter aerogenes, which already produced chromosomal beta-lactamase constitutively, on to varying concentrations of different beta-lactam antibiotics. Frequencies of mutation varied from 10(-5) to 10(-8), depending upon the particular antibiotic and concentration used for selection. Only minor variations in beta-lactamase specific activities were observed and these could not be directly correlated with changes in resistance when compared with the original strain. In the majority of mutants, the selection of an enhanced level of resistance to cefotaxime was associated with a significant increase in resistance to imipenem, but no increase in resistance to the non-beta-lactam antibiotics tested was observed. Examination of outer membrane protein profiles revealed a number of complex changes in the mutants when directly compared to the original strain. In one mutant imipenem/cefotaxime resistance was directly associated with almost total loss of a 42K protein which was non-covalently associated with peptidoglycan and therefore possibly a porin protein.