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Escherichia coli resistance to β-lactam antibiotics through a decrease in the affinity of a target for lethality

Naturevolume 274pages713715 (1978) | Download Citation



CLINICAL isolates of bacteria that have gained resistance to β-lactam antibiotics (penicillins, cephalosporins and related compounds) often arise by the acquisition of a plasmid that produces a β-lactamase1,2. An increase in β-lactamase activity has also been shown to cause resistance in some mutants isolated in the laboratory3. In other cases, β-lactamase activity is not the cause of resistance and, at least in Gram-negative bacteria, alteration of the cell envelope resulting in decreased penetration of the antibiotic to the targets responsible for lethality in the cytoplasmic membrane has been proposed3,4. For several groups of antibiotics resistance has been shown to occur by a decrease in the affinity of the target for lethality for the antibiotic5–9 but, although this mechanism has been suggested as a possible cause of resistance to β-lactam antibiotics, no examples have been reported. The lethality targets for β-lactam antibiotics in Escherichia coli have recently been identified and I report here the characterisation of a mutant that has gained resistance to some β-lactams by a decrease in the affinity of such a target.

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  1. Department of Genetics, University of Leicester, Leicester, UK



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