title: The fdxA ferredoxin gene can down-regulate frxA nitroreductase gene expression and is essential in many strains of Helicobacter pylori.
abstract: Very few examples of metabolic regulation are known in the gastric pathogen Helicobacter pylori. An unanticipated case was suggested, however, upon finding two types of metronidazole (Mtz)-susceptible strains: type I, in which frxA (which encodes a nitroreductase that contributes to Mtz susceptibility) is quiescent, and type II, in which frxA is well expressed. Here we report that inactivation of the fdxA ferredoxin gene (hp277) in type I strains resulted in high-level frxA expression (in effect, making them type II). However, fdxA null derivatives were obtained from only 6 of 32 type I strains tested that were readily transformed with an frxA::aphA marker. This suggested that fdxA is often essential. This essentiality was overcome in 4 of 20 strains by inactivating frxA, which suggested both that frxA overexpression is potentially deleterious and also that fdxA has additional, often vital roles. With type II strains, in contrast, fdxA null derivatives were obtained in 20 of 23 cases tested. Thus, fdxA is dispensable in most strains that normally exhibit (and tolerate) strong frxA expression. We propose that restraint of frxA expression helps maintain balanced metabolic networks in most type I strains, that other homeostatic mechanisms predominate in type II strains, and that these complex results constitute a phenotypic manifestation of H. pylori's great genetic diversity.
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: Asish K
authors.initials: AK
authors.lastname: Mukhopadhyay
authors.forename: Jin-Yong
authors.initials: JY
authors.lastname: Jeong
authors.forename: Daiva
authors.initials: D
authors.lastname: Dailidiene
authors.forename: Paul S
authors.initials: PS
authors.lastname: Hoffman
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Berg
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D015536:Down-Regulation; D005288:Ferredoxins / Q000172:deficiency / Q000235:genetics*; D005798:Genes, Bacterial; D016480:Helicobacter pylori / Q000187:drug effects / Q000201:enzymology / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008795:Metronidazole / Q000494:pharmacology; D009154:Mutation; D009601:Nitroreductases / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D005288:Ferredoxins; D008795:Metronidazole; D009601:Nitroreductases; C413454:flavin nitroreductase