title: Outer membrane permeability barrier in Escherichia coli mutants that are defective in the late acyltransferases of lipid A biosynthesis.
abstract: The tight packing of six fatty acids in the lipid A constituent of lipopolysaccharide (LPS) has been proposed to contribute to the unusually low permeability of the outer membrane of gram-negative enteric bacteria to hydrophobic antibiotics. Here it is shown that the Escherichia coli msbB mutant, which elaborates defective, penta-acylated lipid A, is practically as resistant to a representative set of hydrophobic solutes (rifampin, fusidic acid, erythromycin, clindamycin, and azithromycin) as the parent-type control strain. 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 oligosaccharide 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 A, was still less susceptible than the rfa mutant. These findings indicate that hexa-acylated lipid A is not a prerequisite for the normal function of the outer membrane permeability barrier.
authors.affiliation: Division of Bacteriology and Immunology, Helsinki University Central Hospital, Helsinki, Finland. Martti.Vaara@Helsinki.fi
authors.forename: M
authors.initials: M
authors.lastname: Vaara
authors.forename: M
authors.initials: M
authors.lastname: Nurminen
mesh_terms: D000217:Acyltransferases / Q000502:physiology*; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics; D002463:Cell Membrane Permeability; D004926:Escherichia coli / Q000378:metabolism*; D008050:Lipid A / Q000096:biosynthesis*; D009154:Mutation
chemical_list: D000900:Anti-Bacterial Agents; D008050:Lipid A; D000217:Acyltransferases