The Helicobacter pylori flaA1 and wbpB genes control lipopolysaccharide and flagellum synthesis and function.
flaA1 and wbpB are conserved genes with unknown biological function in Helicobacter pylori. Since both genes are predicted to be involved in lipopolysaccharide (LPS) biosynthesis, flagellum assembly, or protein glycosylation, they could play an important role in the pathogenesis of H. pylori. To determine their biological role, both genes were disrupted in strain NCTC 11637. Both mutants exhibited altered LPS, with loss of most O-antigen and core modification, and increased sensitivity to sodium dodecyl sulfate compared to wild-type bacteria. These defects could be complemented in a gene-specific manner. Also, flaA1 could complement these defects in the wbpB mutant, suggesting a potential redundancy of the reductase activity encoded by both genes. Both mutants were nonmotile, although the wbpB mutant still produced flagella. The defect in the flagellum functionality of this mutant was not due to a defect in flagellin glycosylation since flagellins from wild-type strain NCTC 11637 were shown not to be glycosylated. The flaA1 mutant produced flagellins but no flagellum. Overall, the similar phenotypes observed for both mutants and the complementation of the wbpB mutant by flaA1 suggest that both genes belong to the same biosynthesis pathway. The data also suggest that flaA1 and wbpB are at the interface between several pathways that govern the expression of different virulence factors. We propose that FlaA1 and WbpB synthesize sugar derivatives dedicated to the glycosylation of proteins which are involved in LPS and flagellum production and that glycosylation regulates the activity of these proteins.
Merkx-Jacques
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Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada.
Obhi
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RK
Bethune
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Creuzenet
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C
D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D005407:Flagella / Q000378:metabolism / Q000502:physiology*; D005408:Flagellin / Q000096:biosynthesis*; D005798:Genes, Bacterial / Q000502:physiology*; D006031:Glycosylation; D016480:Helicobacter pylori / Q000235:genetics* / Q000472:pathogenicity; D006836:Hydro-Lyases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008070:Lipopolysaccharides / Q000096:biosynthesis*; D009154:Mutation; D010088:Oxidoreductases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014774:Virulence / Q000235:genetics
D001426:Bacterial Proteins; C417241:FlaA1 protein, Helicobacter pylori; D008070:Lipopolysaccharides; D005408:Flagellin; C067138:flaA protein, bacteria; D010088:Oxidoreductases; D006836:Hydro-Lyases