Escherichia coli msbB gene as a virulence factor and a therapeutic target

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 li pid A. Although such mutant E. coli cells and their purified LPS have a gre atly reduced ability to stimulate human immune cells, a minor reduction in the mouse inflammatory response is observed. When the msbB mutation is tran sferred into a clinical isolate of E. coli, there is a significant loss in virulence, as assessed bu 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 virul ence factor in a murine model off. coli pathogenicity. In the genetic backg round of the clinical E. coli isolate, the msbB mutation also results in fi lamentation of the cells at 37 degrees C but not at 30 degrees C, a reducti on in the level of the Iii 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 virulen ce. The demonstration that the inhibition of msbB gene function reduces the virulence of E. coli in a mouse infection model warrants further investiga tion of the msbB gene product as a novel target for antibiotic therapy.