title: Hybrid cluster proteins and flavodiiron proteins afford protection to Desulfovibrio vulgaris upon macrophage infection.
abstract: Desulfovibrio species are Gram-negative anaerobic sulfate-reducing bacteria that colonize the human gut. Recently, Desulfovibrio spp. have been implicated in gastrointestinal diseases and shown to stimulate the epithelial immune response, leading to increased production of inflammatory cytokines by macrophages. Activated macrophages are key cells of the immune system that impose nitrosative stress during phagocytosis. Hence, we have analyzed the in vitro and in vivo responses of Desulfovibrio vulgaris Hildenborough to nitric oxide (NO) and the role of the hybrid cluster proteins (HCP1 and HCP2) and rubredoxin oxygen oxidoreductases (ROO1 and ROO2) in NO protection. Among the four genes, hcp2 was the gene most highly induced by NO, and the hcp2 transposon mutant exhibited the lowest viability under conditions of NO stress. Studies in murine macrophages revealed that D. vulgaris survives incubation with these phagocytes and triggers NO production at levels similar to those stimulated by the cytokine gamma interferon (IFN-γ). Furthermore, D. vulgaris hcp and roo mutants exhibited reduced viability when incubated with macrophages, revealing that these gene products contribute to the survival of D. vulgaris during macrophage infection.
authors.affiliation: Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Oeiras, Portugal.
authors.forename: Mafalda C O
authors.initials: MC
authors.lastname: Figueiredo
authors.forename: Susana A L
authors.initials: SA
authors.lastname: Lobo
authors.forename: Sara H
authors.initials: SH
authors.lastname: Sousa
authors.forename: Fábio P
authors.initials: FP
authors.lastname: Pereira
authors.forename: Judy D
authors.initials: JD
authors.lastname: Wall
authors.forename: Lígia S
authors.initials: LS
authors.lastname: Nobre
authors.forename: Lígia M
authors.initials: LM
authors.lastname: Saraiva
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D016969:Desulfovibrio vulgaris / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D045824:Desulfovibrionaceae Infections / Q000276:immunology / Q000382:microbiology*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability; D016254:Mutagenesis, Insertional; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D009573:Nitrites / Q000032:analysis / Q000378:metabolism; D018384:Oxidative Stress; D010641:Phenotype; D013312:Stress, Physiological
chemical_list: D001426:Bacterial Proteins; D007506:Iron-Sulfur Proteins; D009573:Nitrites; C075199:prismane protein, Desulfovibrio vulgaris; D009569:Nitric Oxide; C023091:rubredoxin-NAD+ reductase; D009247:NADH, NADPH Oxidoreductases
references.citation: Appl Environ Microbiol. 2009 Dec;75(24):7682-91
references.pmid: 19837844
references.citation: J Bacteriol. 2012 Jul;194(14):3611-7
references.pmid: 22563051
references.citation: J Bacteriol. 2006 Apr;188(8):2745-51
references.pmid: 16585735
references.citation: Infect Immun. 2003 Jun;71(6):3196-205
references.pmid: 12761099
references.citation: Environ Microbiol. 2005 Sep;7(9):1461-5
references.pmid: 16104868
references.citation: J Bacteriol. 2006 Sep;188(17):6253-60
references.pmid: 16923892
references.citation: Antimicrob Agents Chemother. 2009 Dec;53(12):5308-11
references.pmid: 19786606
references.citation: J Biol Chem. 2006 Oct 27;281(43):32445-50
references.pmid: 16928682
references.citation: J Biol Chem. 1997 Sep 5;272(36):22502-8
references.pmid: 9278402
references.citation: Mol Oral Microbiol. 2010 Jun;25(3):226-35
references.pmid: 20536750
references.citation: Dis Colon Rectum. 2010 Nov;53(11):1530-6
references.pmid: 20940602
references.citation: Med Mal Infect. 2011 May;41(5):267-8
references.pmid: 21208758
references.citation: Annu Rev Immunol. 1997;15:323-50
references.pmid: 9143691
references.citation: J Bacteriol. 2002 Nov;184(21):5898-902
references.pmid: 12374823
references.citation: J Biol Inorg Chem. 2002 Apr;7(4-5):514-25
references.pmid: 11941509
references.citation: Nat Struct Biol. 2000 Nov;7(11):1041-5
references.pmid: 11062560
references.citation: J Bacteriol. 2004 Dec;186(23):7944-50
references.pmid: 15547266
references.citation: Anaerobe. 2010 Jun;16(3):229-33
references.pmid: 20159048
references.citation: Eur J Clin Microbiol Infect Dis. 1999 Aug;18(8):602-3
references.pmid: 10517202
references.citation: Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):8841-8
references.pmid: 10922044
references.citation: Biochem Soc Trans. 2011 Jan;39(1):213-5
references.pmid: 21265775
references.citation: Appl Environ Microbiol. 2012 Feb;78(4):1168-77
references.pmid: 22156435
references.citation: J Biol Inorg Chem. 2009 Jun;14(5):703-10
references.pmid: 19241093
references.citation: ISME J. 2010 Nov;4(11):1386-97
references.pmid: 20445634
references.citation: Environ Microbiol. 2012 Oct;14(10):2711-25
references.pmid: 22947039
references.citation: J Biol Chem. 2004 Oct 29;279(44):45485-94
references.pmid: 15322098
references.citation: Environ Microbiol. 2009 Apr;11(4):981-91
references.pmid: 19077010
references.citation: FEMS Microbiol Lett. 2011 Dec;325(2):99-107
references.pmid: 22029434
references.citation: Appl Environ Microbiol. 2006 Jun;72(6):4370-81
references.pmid: 16751553
references.citation: J Biol Chem. 2005 Jan 28;280(4):2636-43
references.pmid: 15546870
references.citation: FEMS Immunol Med Microbiol. 2012 Jun;65(1):55-68
references.pmid: 22309113
references.citation: J Biol Inorg Chem. 2003 May;8(5):540-548
references.pmid: 12764602
references.citation: Anaerobe. 2012 Aug;18(4):454-8
references.pmid: 22706208
references.citation: Adv Microb Physiol. 2004;49:77-129
references.pmid: 15518829
references.citation: Science. 2012 Apr 27;336(6080):470-3
references.pmid: 22539721