title: Vitamin B6 is required for full motility and virulence in Helicobacter pylori.
abstract: Despite recent advances in our understanding of how Helicobacter pylori causes disease, the factors that allow this pathogen to persist in the stomach have not yet been fully characterized. To identify new virulence factors in H. pylori, we generated low-infectivity variants of a mouse-colonizing H. pylori strain using the classical technique of in vitro attenuation. The resulting variants and their highly infectious progenitor bacteria were then analyzed by global gene expression profiling. The gene expression levels of five open reading frames (ORFs) were significantly reduced in low-infectivity variants, with the most significant changes observed for ORFs HP1583 and HP1582. These ORFs were annotated as encoding homologs of the Escherichia coli vitamin B(6) biosynthesis enzymes PdxA and PdxJ. Functional complementation studies with E. coli confirmed H. pylori PdxA and PdxJ to be bona fide homologs of vitamin B(6) biosynthesis enzymes. Importantly, H. pylori PdxA was required for optimal growth in vitro and was shown to be essential for chronic colonization in mice. In addition to having a well-known metabolic role, vitamin B(6) is necessary for the synthesis of glycosylated flagella and for flagellum-based motility in H. pylori. Thus, for the first time, we identify vitamin B(6) biosynthesis enzymes as novel virulence factors in bacteria. Interestingly, pdxA and pdxJ orthologs are present in a number of human pathogens, but not in mammalian cells. We therefore propose that PdxA/J enzymes may represent ideal candidates for therapeutic targets against bacterial pathogens.
authors.affiliation: Department of Microbiology, Monash University, Melbourne, Australia.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Grubman
authors.forename: Alexandra
authors.initials: A
authors.lastname: Phillips
authors.forename: Marie
authors.initials: M
authors.lastname: Thibonnier
authors.forename: Maria
authors.initials: M
authors.lastname: Kaparakis-Liaskos
authors.forename: Chad
authors.initials: C
authors.lastname: Johnson
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Thiberge
authors.forename: Fiona J
authors.initials: FJ
authors.lastname: Radcliff
authors.forename: Chantal
authors.initials: C
authors.lastname: Ecobichon
authors.forename: Agnès
authors.initials: A
authors.lastname: Labigne
authors.forename: Hilde
authors.initials: H
authors.lastname: de Reuse
authors.forename: George L
authors.initials: GL
authors.lastname: Mendz
authors.forename: Richard L
authors.initials: RL
authors.lastname: Ferrero
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005753:Gastric Mucosa / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D016481:Helicobacter Infections / Q000382:microbiology*; D016480:Helicobacter pylori / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D014774:Virulence; D025101:Vitamin B 6 / Q000096:biosynthesis*
chemical_list: D001426:Bacterial Proteins; D025101:Vitamin B 6