Multiply resistant mutants of Enterobacter cloacae selected by beta-lactam antibiotics.

Mutants of Enterobacter cloacae, selected in vitro with ceftriaxone, ceftazidime, carumonam, or aztreonam, fell into several distinct classes. Three mutants highly resistant to nearly all beta-lactam antibiotics were stably derepressed for beta-lactamase production. Although no other changes could be detected, virulence in a mouse septicemia model was decreased in two of these mutants. One mutant, 908-Ssi, showed selectively decreased susceptibility to ampicillin and cefotetan. A change in beta-lactamase expression was thought to be responsible for this. Alterations in the production of two outer membrane proteins with molecular sizes of 36.5 and 39 kilodaltons were responsible for multiple antibiotic resistance in two mutants, both of which acquired a low level of resistance to beta-lactam antibiotics. Whereas one of the mutants, AMA-R, simultaneously acquired resistance to chloramphenicol and trimethoprim, the other, AZT-R, became hypersusceptible to these and other hydrophobic agents. Both strains had drastically reduced virulence in mice.