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Infection and Immunity, December 1999, p. 6583-6590, Vol. 67, No. 12
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Escherichia coli msbB Gene as a Virulence Factor and a Therapeutic Target

John E. Somerville Jr.,1 Linda Cassiano,1 and Richard P. Darveau2,*

Inflammation Department, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543,1 and Department of Periodontics, University of Washington, Seattle, Washington 981952

Received 2 April 1999/Returned for modification 11 June 1999/Accepted 14 September 1999

A mutation in the msbB gene of Escherichia coli results in the synthesis of E. coli lipopolysaccharide (LPS) that lacks the myristic acid moiety of lipid A. Although such mutant E. coli cells and their purified LPS have a greatly reduced ability to stimulate human immune cells, a minor reduction in the mouse inflammatory response is observed. When the msbB mutation is transferred into a clinical isolate of E. coli, there is a significant loss in virulence, as assessed by lethality in BALB/c mice. When a cloned msbB gene is provided to functionally complement the msbB mutant, virulence returns, providing direct evidence that the msbB gene product is an important virulence factor in a murine model of E. coli pathogenicity. In the genetic background of the clinical E. coli isolate, the msbB mutation also results in filamentation of the cells at 37°C but not at 30°C, a reduction in the level of the K1 capsule, an increase in the level of complement C3 deposition, and an increase in both opsonic and nonopsonic phagocytosis of the msbB mutant, phenotypes that can help to explain the loss in virulence. The demonstration that the inhibition of msbB gene function reduces the virulence of E. coli in a mouse infection model warrants further investigation of the msbB gene product as a novel target for antibiotic therapy.

* Corresponding author. Mailing address: Department of Periodontics, University of Washington, Box 357444, Seattle, WA 98195-7444. Phone: (206) 543-9514. Fax: (206) 616-7478. E-mail: rdarveau{at}u.washington.edu.

Infection and Immunity, December 1999, p. 6583-6590, Vol. 67, No. 12
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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