title: Comparative genomic analysis of Brucella melitensis vaccine strain M5 provides insights into virulence attenuation.
abstract: The Brucella melitensis vaccine strain M5 is widely used to prevent and control brucellosis in animals. In this study, we determined the whole-genome sequence of M5, and conducted a comprehensive comparative analysis against the whole-genome sequence of the virulent strain 16 M and other reference strains. This analysis revealed 11 regions of deletion (RDs) and 2 regions of insertion (RIs) within the M5 genome. Among these regions, the sequences encompassed in 5 RDs and 1 RI showed consistent variation, with a large deletion between the M5 and the 16 M genomes. RD4 and RD5 showed the large diversity among all Brucella genomes, both in RD length and RD copy number. Thus, RD4 and RD5 are potential sites for typing different Brucella strains. Other RD and RI regions exhibited multiple single nucleotide polymorphisms (SNPs). In addition, a genome fragment with a 56 kb rearrangement was determined to be consistent with previous studies. Comparative genomic analysis indicated that genomic island inversion in Brucella was widely present. With the genetic pattern common among all strains analyzed, these 2 RDs, 1 RI, and one inversion region are potential sites for detection of genomic differences. Several SNPs of important virulence-related genes (motB, dhbC, sfuB, dsbAB, aidA, aroC, and lysR) were also detected, and may be used to determine the mechanism of virulence attenuation. Collectively, this study reveals that comparative analysis between wild-type and vaccine strains can provide resources for the study of virulence and microevolution of Brucella.
authors: State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Beijing, China.
authors: Hai
authors: H
authors: Jiang
authors: Pengcheng
authors: P
authors: Du
authors: Wen
authors: W
authors: Zhang
authors: Heng
authors: H
authors: Wang
authors: Hongyan
authors: H
authors: Zhao
authors: Dongri
authors: D
authors: Piao
authors: Guozhong
authors: G
authors: Tian
authors: Chen
authors: C
authors: Chen
authors: Buyun
authors: B
authors: Cui
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D058947:Bacterial Secretion Systems / Q000235:genetics; D001428:Bacterial Vaccines / Q000276:immunology*; D001692:Biological Transport / Q000235:genetics; D017347:Brucella melitensis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity*; D050260:Carbohydrate Metabolism / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D016680:Genome, Bacterial / Q000235:genetics; D023281:Genomics; D008670:Metals / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics; D009584:Nitrogen / Q000378:metabolism; D016366:Open Reading Frames / Q000235:genetics; D010084:Oxidation-Reduction; D020641:Polymorphism, Single Nucleotide; D012329:RNA, Bacterial / Q000235:genetics; D014774:Virulence / Q000235:genetics / Q000276:immunology; D037521:Virulence Factors / Q000235:genetics
chemical_list: D000596:Amino Acids; D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D001428:Bacterial Vaccines; D004269:DNA, Bacterial; D008670:Metals; D018832:Molecular Chaperones; D012329:RNA, Bacterial; D037521:Virulence Factors; D009584:Nitrogen
references: PLoS One. 2008 May 14;3(5):e2193
references: 18478107
references: Nucleic Acids Res. 1999 Dec 1;27(23):4636-41
references: 10556321
references: Mol Plant Microbe Interact. 2008 Aug;21(8):1036-45
references: 18616400
references: Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3027-30
references: 12631703
references: Vaccine. 1994 Apr;12(5):435-8
references: 7912870
references: Vaccine. 2002 Jun 7;20(19-20):2546-50
references: 12057611
references: Genome Res. 2003 Sep;13(9):2178-89
references: 12952885
references: Nucleic Acids Res. 2002 Jun 1;30(11):2478-83
references: 12034836
references: Clin Diagn Lab Immunol. 1999 Sep;6(5):760-4
references: 10473532
references: Prev Vet Med. 1997 Aug;31(3-4):275-83
references: 9234451
references: BMC Microbiol. 2009 May 13;9:92
references: 19439075
references: PLoS One. 2010 Apr 21;5(4):e10216
references: 20422049
references: Infect Immun. 2001 Jul;69(7):4528-35
references: 11401996
references: Vet Microbiol. 2002 Dec 20;90(1-4):165-82
references: 12414142
references: Infect Immun. 2005 Sep;73(9):5578-86
references: 16113274
references: Infect Immun. 1996 Nov;64(11):4549-56
references: 8890205
references: Infect Immun. 2012 May;80(5):1783-93
references: 22392933
references: Infect Immun. 1996 Jun;64(6):2188-92
references: 8675325
references: Microb Pathog. 2002 May;32(5):239-48
references: 12071680
references: Infect Immun. 2001 Dec;69(12):7736-42
references: 11705955
references: Vet Microbiol. 2002 Dec 20;90(1-4):249-61
references: 12414147
references: Annu Rev Microbiol. 1993;47:597-626
references: 8257110
references: Infect Immun. 2000 Mar;68(3):1297-303
references: 10678941
references: Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1544-9
references: 11830669
references: Genomics Proteomics Bioinformatics. 2006 Nov;4(4):259-63
references: 17531802
references: Microbiology (Reading). 2005 Jan;151(Pt 1):219-231
references: 15632440
references: FEMS Microbiol Lett. 2004 Feb 9;231(1):1-12
references: 14979322
references: J Bacteriol. 2011 Jul;193(14):3674-5
references: 21602346
references: Emerg Infect Dis. 2010 Dec;16(12):2001-3
references: 21122244
references: Infect Immun. 2003 Mar;71(3):1481-90
references: 12595466
references: Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15711-6
references: 12438693
references: PLoS One. 2012;7(3):e31747
references: 22403618
references: Infect Immun. 2003 Apr;71(4):1794-803
references: 12654793
references: FEMS Microbiol Lett. 1994 Sep 1;121(3):337-42
references: 7926690
references: J Appl Microbiol. 2005;98(6):1270-81
references: 15916641
references: Infect Immun. 2003 Apr;71(4):2110-9
references: 12654833
references: Infect Immun. 2000 Nov;68(11):6329-36
references: 11035742
references: Met Ions Biol Syst. 1998;35:67-145
references: 9444760
references: Infect Immun. 2004 Oct;72(10):5783-90
references: 15385478
references: J Bacteriol. 2011 Jun;193(11):2904-5
references: 21478357
references: Cell Microbiol. 2001 Mar;3(3):159-68
references: 11260139
references: Vet Res. 1998 May-Aug;29(3-4):255-74
references: 9689741