title: A critical role for the cccA gene product, cytochrome c2, in diverting electrons from aerobic respiration to denitrification in Neisseria gonorrhoeae.
abstract: Neisseria gonorrhoeae is a microaerophile that, when oxygen availability is limited, supplements aerobic respiration with a truncated denitrification pathway, nitrite reduction to nitrous oxide. We demonstrate that the cccA gene of Neisseria gonorrhoeae strain F62 (accession number NG0292) is expressed, but the product, cytochrome c2, accumulates to only low levels. Nevertheless, a cccA mutant reduced nitrite at about half the rate of the parent strain. We previously reported that cytochromes c4 and c5 transfer electrons to cytochrome oxidase cbb3 by two independent pathways and that the CcoP subunit of cytochrome oxidase cbb3 transfers electrons to nitrite. We show that mutants defective in either cytochrome c4 or c5 also reduce nitrite more slowly than the parent. By combining mutations in cccA (Δc2), cycA (Δc4), cycB (Δc5), and ccoP (ccoP-C368A), we demonstrate that cytochrome c2 is required for electron transfer from cytochrome c4 via the third heme group of CcoP to the nitrite reductase, AniA, and that cytochrome c5 transfers electrons to nitrite reductase by an independent pathway. We propose that cytochrome c2 forms a complex with cytochrome oxidase. If so, the redox state of cytochrome c2 might regulate electron transfer to nitrite or oxygen. However, our data are more consistent with a mechanism in which cytochrome c2 and the CcoQ subunit of cytochrome oxidase form alternative complexes that preferentially catalyze nitrite and oxygen reduction, respectively. Comparison with the much simpler electron transfer pathway for nitrite reduction in the meningococcus provides fascinating insights into niche adaptation within the pathogenic neisseriae.
authors.affiliation: School of Biosciences, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Hopper
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Cole
mesh_terms: D000222:Adaptation, Physiological; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D019295:Computational Biology; D003574:Cytochrome c Group / Q000235:genetics / Q000378:metabolism; D045362:Cytochromes c2 / Q000235:genetics / Q000378:metabolism*; D058440:Denitrification; D004579:Electron Transport; D015964:Gene Expression Regulation, Bacterial; D005816:Genetic Complementation Test; D006418:Heme / Q000378:metabolism; D009344:Neisseria gonorrhoeae / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D009573:Nitrites / Q000378:metabolism*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins; D015203:Reproducibility of Results; D017384:Sequence Deletion
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D003574:Cytochrome c Group; D009573:Nitrites; D011993:Recombinant Fusion Proteins; C077531:aniA protein, Neisseria gonorrhoeae; C034186:cytochrome C4; D006418:Heme; C046450:cytochrome C5; D045362:Cytochromes c2; D010100:Oxygen
references.citation: Mol Microbiol. 2005 Oct;58(2):520-32
references.pmid: 16194237
references.citation: Infect Immun. 1987 Jun;55(6):1359-64
references.pmid: 3106220
references.citation: Mol Microbiol. 1998 Nov;30(4):697-710
references.pmid: 10094619
references.citation: Infect Immun. 2005 Jun;73(6):3322-9
references.pmid: 15908358
references.citation: Infect Immun. 1992 Nov;60(11):4704-8
references.pmid: 1398981
references.citation: Infect Immun. 1984 Oct;46(1):176-81
references.pmid: 6434425
references.citation: Mol Microbiol. 2000 Aug;37(4):839-55
references.pmid: 10972806
references.citation: Microbiology (Reading). 1997 May;143 ( Pt 5):1757-1764
references.pmid: 9168625
references.citation: Nature. 2000 Mar 30;404(6777):502-6
references.pmid: 10761919
references.citation: Microbiology (Reading). 2006 Nov;152(Pt 11):3227-3237
references.pmid: 17074894
references.citation: J Bacteriol. 2002 Jun;184(11):2987-93
references.pmid: 12003939
references.citation: J Bacteriol. 2007 Feb;189(3):1138-44
references.pmid: 17122348
references.citation: Am J Clin Nutr. 2009 Jul;90(1):1-10
references.pmid: 19439460
references.citation: J Bacteriol. 2008 Sep;190(17):6035-6
references.pmid: 18586945
references.citation: Biochem J. 2005 Jun 1;388(Pt 2):545-53
references.pmid: 15689189
references.citation: Biochem J. 2003 Aug 1;373(Pt 3):865-73
references.pmid: 12720546
references.citation: Infect Immun. 2000 Sep;68(9):5241-6
references.pmid: 10948150
references.citation: Plasmid. 2005 Nov;54(3):191-218
references.pmid: 16024078
references.citation: J Mol Biol. 2006 Feb 3;355(5):989-1004
references.pmid: 16343536
references.citation: Gene. 1995 Dec 1;166(1):101-4
references.pmid: 8529870
references.citation: J Bacteriol. 1999 Jan;181(2):541-51
references.pmid: 9882668
references.citation: Biochim Biophys Acta. 2004 Apr 12;1655(1-3):388-99
references.pmid: 15100055
references.citation: Microbiology (Reading). 2012 Jun;158(Pt 6):1402-1413
references.pmid: 22493300
references.citation: J Bacteriol. 2005 Oct;187(19):6849-51
references.pmid: 16166549
references.citation: Microbiol Mol Biol Rev. 1997 Dec;61(4):533-616
references.pmid: 9409151
references.citation: FEMS Microbiol Lett. 2009 Dec;301(2):232-40
references.pmid: 19889029
references.citation: EFSA J. 2008 Jul 21;6(7):653
references.pmid: 37213838
references.citation: FEMS Microbiol Lett. 2009 Oct;299(1):86-94
references.pmid: 19686347
references.citation: J Infect Dis. 1990 Feb;161(2):336-9
references.pmid: 1688906
references.citation: Microbiology (Reading). 2008 Sep;154(Pt 9):2857-2864
references.pmid: 18757819
references.citation: J Infect Dis. 2004 Jul 1;190(1):136-47
references.pmid: 15195253
references.citation: Biochim Biophys Acta. 2000 Aug 15;1459(2-3):346-55
references.pmid: 11004450
references.citation: J Biol Chem. 2002 May 3;277(18):16220-8
references.pmid: 11864982
references.citation: Infect Immun. 2005 Dec;73(12):8444-8
references.pmid: 16299348
references.citation: J Gen Microbiol. 1984 May;130(5):1279-84
references.pmid: 6381645
references.citation: Microb Pathog. 1988 Nov;5(5):381-90
references.pmid: 3148817
references.citation: Anal Biochem. 1976 Sep;75(1):168-76
references.pmid: 822747
references.citation: Microbiology (Reading). 2009 Dec;155(Pt 12):4093-4103
references.pmid: 19762442
references.citation: Free Radic Biol Med. 2006 Nov 1;41(9):1404-12
references.pmid: 17023267
references.citation: Clin Microbiol Rev. 1989 Apr;2 Suppl:S1-4
references.pmid: 2470496
references.citation: J Bacteriol. 2008 Aug;190(16):5576-86
references.pmid: 18556791
references.citation: Mol Gen Genet. 1997 Nov;256(5):525-32
references.pmid: 9413436
references.citation: BMC Microbiol. 2009 Dec 09;9:252
references.pmid: 20003185
references.citation: J Mol Biol. 2002 Feb 1;315(5):1111-27
references.pmid: 11827480
references.citation: PLoS Pathog. 2010 Aug 19;6(8):e1001055
references.pmid: 20808844
references.citation: J Bacteriol. 2010 May;192(9):2395-406
references.pmid: 20154126
references.citation: Nat Protoc. 2006;1(1):418-28
references.pmid: 17406264