Affiliation:
1. Division of Bacteriology and Immunology, Helsinki University Central Hospital,1
2. Department of Bacteriology, University of Helsinki,2 and
3. Department of Bacteriology, National Public Health Institute,3 Helsinki, Finland
Abstract
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.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
109 articles.
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