Outer membrane permeability barrier in Escherichia coli mutants that are defective in the late acyltransferases of lipid A biosynthesis

The tight packing of six fatty acids in the lipid A constituent of lipopoly saccharide (LPS) has been proposed to contribute to the unusually low perme ability of the outer membrane of gram-negative enteric bacteria to hydropho bic antibiotics. Here it is shown that the Escherichia coil msbB mutant, wh ich elaborates defective, penta-acylated lipid A, is practically as resista nt to a representative set of hydrophobic solutes (rifampin, fusidic acid, erythromycin, clindamycin, and azithromycin) as the parent-type control str ain. The susceptibility index, i.e., the approximate ratio between the MIC for the msbB mutant and that for the parent-type control, was maximally 2.7 -fold, In comparison, the rfa mutant defective in the deep core oligosaccha ride part of LPS displayed indices ranging from 20 to 64. The lpxA and lpxD lipid A mutants had indices higher than 512, Furthermore, the msbB mutant was resistant to glycopeptides (vancomycin, teicoplanin), whereas the rfa, lpxA, and lpxD mutants were susceptible. The msbB htrB double mutant, which elaborates even-more defective, partially tetra-acylated lipid Al was stil l less susceptible than the rfa mutant. These findings indicate that hexa-a cylated lipid A is not a prerequisite for the normal function of the outer membrane permeability barrier.