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 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 degrees C but not at 30 degrees 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.
Somerville
J E
JE
Inflammation Department, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543, USA.
Cassiano
L
L
Darveau
R P
RP
D000217:Acyltransferases; D000818:Animals; D016667:Bacterial Capsules / Q000378:metabolism; D003176:Complement C3 / Q000276:immunology; D004926:Escherichia coli / Q000235:genetics* / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000382:microbiology* / Q000401:mortality; D029968:Escherichia coli Proteins; D006801:Humans; D008050:Lipid A / Q000031:analogs & derivatives* / Q000235:genetics / Q000502:physiology; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D016296:Mutagenesis; D009895:Opsonin Proteins / Q000276:immunology; D010587:Phagocytosis; D014774:Virulence / Q000235:genetics
D003176:Complement C3; D029968:Escherichia coli Proteins; D008050:Lipid A; D008070:Lipopolysaccharides; D009895:Opsonin Proteins; D000217:Acyltransferases; C097895:MsbB protein, E coli