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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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