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Antimicrobial Agents and Chemotherapy, June 1999, p. 1459-1462, Vol. 43, No. 6
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Outer Membrane Permeability Barrier in Escherichia coli Mutants That Are Defective in the Late Acyltransferases of Lipid A Biosynthesis

Martti Vaara1,2,3,* and Marjatta Nurminen1,3

Division of Bacteriology and Immunology, Helsinki University Central Hospital,1 Department of Bacteriology, University of Helsinki,2 and Department of Bacteriology, National Public Health Institute,3 Helsinki, Finland

Received 13 October 1998/Returned for modification 28 January 1999/Accepted 28 March 1999

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.


* Corresponding author. Mailing address: Department of Bacteriology, University of Helsinki, Haartmaninkatu 3, 00014 Helsinki, Finland. Phone: 358-9-1912-6302. Fax: 358-9-1912-6382. E-mail: Martti.Vaara{at}Helsinki.fi.


Antimicrobial Agents and Chemotherapy, June 1999, p. 1459-1462, Vol. 43, No. 6
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



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