THE LIPID-A BIOSYNTHESIS MUTATION LPXA2 OF ESCHERICHIA-COLI RESULTS IN DRASTIC ANTIBIOTIC SUPERSUSCEPTIBILITY

The conditionally lethal lpxA2 mutant of Escherichia coli, which lacks detectable UDP-N-acetylglucosamine acyltransferase activity and which produces greatly reduced amounts of lipid A after a shift to 42-degrees-C (S. Galloway and C. R. H. Raetz, J. Biol. Chem. 265:6394-6402, 1990), was found to be, at conditions which promote normal growth, remarkably susceptible to a number of antibiotics. The MICs of hydrophobic antibiotics, such as rifampin, erythromycin, clindamycin, and fusidic acid, were 32- to > 128-fold lower for the lpxA2 strain than for the parent type strain, and those of the peptide antibiotics vancomycin and bacitracin were 32- and 256-fold lower, respectively. Furthermore, the lpxA2 strain was found to be sensitive to hypoosmotic conditions. Comparisons with the other characterized outer membrane permeability mutants, such as the heptose-deficient strains of E. coli and Salmonella typhimurium, the acrA and abs mutants of E. coli, and the ssc-1 and class SS-B mutants of S. typhimurium, indicated that the lpxA2 mutant had characteristically the most antibiotic-supersusceptible phenotype. These findings advocate the possible use of the lpxA2 strain as a tool in various fields of basic and applied bacterial research in which the impermeability of the outer membrane currently poses problems.