Responsiveness to acidity via metal ion regulators mediates virulence in the gastric pathogen Helicobacter pylori

Autor: Bury-Moné, Stéphanie, Thiberge, Jean-Michel, Contreras, Monica, Maitournam, Aboubakar, Labigne, Agnès, De Reuse, Hilde
Přispěvatelé: Pathogénie Bactérienne des Muqueuses, Institut Pasteur [Paris] (IP), Institut de génétique et microbiologie [Orsay] (IGM), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Puces à ADN (Plate-Forme 2) (PF2), Institut Pasteur [Paris]
Jazyk: angličtina
Rok vydání: 2004
Předmět:
MESH: Amidohydrolases
MESH: Hydrogen-Ion Concentration
MESH: Virulence
MESH: Down-Regulation
MESH: Proton-Translocating ATPases
Mice
MESH: Up-Regulation
MESH: Animals
MESH: Ammonia
MESH: Bacterial Proteins
MESH: Gene Expression Regulation
Bacterial
Virulence
Hydrogen-Ion Concentration
Adaptation
Physiological
Urease
Up-Regulation
Proton-Translocating ATPases
[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology
Metals
MESH: Repressor Proteins
MESH: Genes
Bacterial
Sodium-Hydrogen Exchangers
Virulence Factors
MESH: Urease
Down-Regulation
Buffers
MESH: Acids
Amidohydrolases
Helicobacter Infections
MESH: Gene Expression Profiling
Bacterial Proteins
Ammonia
Animals
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
MESH: Mice
MESH: Virulence Factors
MESH: Metals
MESH: Sodium-Hydrogen Antiporter
Helicobacter pylori
Gene Expression Profiling
MESH: Helicobacter Infections
Gene Expression Regulation
Bacterial
MESH: Adaptation
Physiological
Repressor Proteins
Disease Models
Animal
Genes
Bacterial
MESH: Gene Deletion
MESH: Helicobacter pylori
MESH: Buffers
MESH: Disease Models
Animal
Acids
Gene Deletion
Zdroj: Molecular Microbiology
Molecular Microbiology, 2004, 53 (2), pp.623-38. ⟨10.1111/j.1365-2958.2004.04137.x⟩
Molecular Microbiology, Wiley, 2004, 53 (2), pp.623-38. ⟨10.1111/j.1365-2958.2004.04137.x⟩
ISSN: 0950-382X
1365-2958
DOI: 10.1111/j.1365-2958.2004.04137.x⟩
Popis: International audience; The virulence of pathogenic bacteria is dependent on their adaptation to and survival in the stressful conditions encountered in their hosts. Helicobacter pylori exclusively colonizes the acid stomach of primates, making it an ideal study model. Little is known about how H. pylori responds to the moderately acidic conditions encountered at its colonization site, the gastric mucus layer. Thus, we compared gene expression profiles of H. pylori 26695 grown at neutral and acidic pH, and validated the data for a selection of genes by real-time polymerase chain reaction, dot-blots or enzymatic assays. During growth in acidic conditions, 56 genes were upregulated and 45 genes downregulated. We found that acidity is a signal modulating the expression of several virulence factors. Regulation of genes related to metal ion homeostasis suggests protective mechanisms involving diminished transport and enhanced storage. Genes encoding subunits of the F0F1 ATPase and of a newly identified Na+/H+ antiporter (NhaC-HP0946) were downregulated, revealing that this bacterium uses original mechanisms to control proton entry. Five of the upregulated genes encoded proteins controlling intracellular ammonia synthesis, including urease, amidase and formamidase, underlining the major role of this buffering compound in the protection against acidity in H. pylori. Regulatory networks and transcriptome analysis as well as enzymatic assays implicated two metal-responsive transcriptional regulators (NikR and Fur) and an essential two-component response regulator (HP0166, OmpR-like) as effectors of the H. pylori acid response. Finally, a nikR-fur mutant is attenuated in the mouse model, emphasizing the link between response to acidity, metal metabolism and virulence in this gastric pathogen.
Databáze: OpenAIRE
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