PLASMID LOSS FROM GRAM-NEGATIVE BACTERIA EXPOSED TO SUBINHIBITORY CONCENTRATIONS OF BETA-LACTAM DRUGS AND AZITHROMYCIN

The stability of F'lac, pW101 and pHSG298 in Escherichia coli K12 expo sed to subinhibitory concentrations of beta-lactam antibiotics, amikac in and tetracycline was studied. High molecular weight low copy plasmi ds (F'lac and pW101) were eliminated from bacteria treated with PBP-3 binding molecules, while a low molecular weight high copy extrachromos omal element (pHSG298) was not. None of the carbapenem antibiotics, me cillinam, amikacin or tetracycline promoted high rate plasmid loss fro m their hosts. Under the same conditions, plasmid-mediated ampicillin- resistance due to p-lactamase production was also lost from F'lacTn1-c arrying bacteria. In contrast, the high copy R6K plasmid was stably in herited in their hosts with the exception of those organisms treated w ith cefixime. When the same experiments were performed with a Klebsiel la pneumoniae strain induced to form filaments by azithromycin at sub- MICs, F'lacTn1 and pW101 loss was detected, while pHSG298 was stably i nherited. These results confirm previous observations that plasmid sta bility is correlated with cell shape and that recovery is more easily achieved when bacteria undergo an unbalanced division resulting in cel l filamentation.