title: Alkyl hydroperoxide reductase is required for Helicobacter cinaedi intestinal colonization and survival under oxidative stress in BALB/c and BALB/c interleukin-10-/- mice.
abstract: Helicobacter cinaedi, a common human intestinal bacterium, has been implicated in various enteric and systemic diseases in normal and immunocompromised patients. Protection against oxidative stress is a crucial component of bacterium-host interactions. Alkyl hydroperoxide reductase C (AhpC) is an enzyme responsible for detoxification of peroxides and is important in protection from peroxide-induced stress. H. cinaedi possesses a single ahpC, which was investigated with respect to its role in bacterial survival during oxidative stress. The H. cinaedi ahpC mutant had diminished resistance to organic hydroperoxide toxicity but increased hydrogen peroxide resistance compared with the wild-type (WT) strain. The mutant also exhibited an oxygen-sensitive phenotype and was more susceptible to killing by macrophages than the WT strain. In vivo experiments in BALB/c and BALB/c interleukin-10 (IL-10)(-/-) mice revealed that the cecal colonizing ability of the ahpC mutant was significantly reduced. The mutant also had diminished ability to induce bacterium-specific immune responses in vivo, as shown by immunoglobulin (IgG2a and IgG1) serum levels. Collectively, these data suggest that H. cinaedi ahpC not only contributes to protecting the organism against oxidative stress but also alters its pathogenic properties in vivo.
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Nisanart
authors.initials: N
authors.lastname: Charoenlap
authors.forename: Zeli
authors.initials: Z
authors.lastname: Shen
authors.forename: Megan E
authors.initials: ME
authors.lastname: McBee
authors.forename: Suresh
authors.initials: S
authors.lastname: Muthupalani
authors.forename: Gerald N
authors.initials: GN
authors.lastname: Wogan
authors.forename: James G
authors.initials: JG
authors.lastname: Fox
authors.forename: David B
authors.initials: DB
authors.lastname: Schauer
mesh_terms: D000818:Animals; D058491:Bacterial Load; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002432:Cecum / Q000382:microbiology; D005260:Female; D017353:Gene Deletion; D016998:Helicobacter / Q000187:drug effects / Q000201:enzymology / Q000472:pathogenicity*; D016481:Helicobacter Infections / Q000382:microbiology*; D054884:Host-Pathogen Interactions; D006861:Hydrogen Peroxide / Q000633:toxicity; D016753:Interleukin-10 / Q000172:deficiency / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D050296:Microbial Viability; D018384:Oxidative Stress; D010100:Oxygen / Q000633:toxicity; D010544:Peroxidases / Q000235:genetics / Q000378:metabolism*; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; C508609:IL10 protein, human; C556062:IL10 protein, mouse; D037521:Virulence Factors; D016753:Interleukin-10; D006861:Hydrogen Peroxide; D010544:Peroxidases; D054464:Peroxiredoxins; C508531:ahpC protein, Helicobacter pylori; D010100:Oxygen