title: Comparative genomic analyses of Mycoplasma hyopneumoniae pathogenic 168 strain and its high-passaged attenuated strain.
abstract: BACKGROUND
  Mycoplasma hyopneumoniae is the causative agent of porcine enzootic pneumonia (EP), a mild, chronic pneumonia of swine. Despite presenting with low direct mortality, EP is responsible for major economic losses in the pig industry. To identify the virulence-associated determinants of M. hyopneumoniae, we determined the whole genome sequence of M. hyopneumoniae strain 168 and its attenuated high-passage strain 168-L and carried out comparative genomic analyses.
  
  
  RESULTS
  We performed the first comprehensive analysis of M. hyopneumoniae strain 168 and its attenuated strain and made a preliminary survey of coding sequences (CDSs) that may be related to virulence. The 168-L genome has a highly similar gene content and order to that of 168, but is 4,483 bp smaller because there are 60 insertions and 43 deletions in 168-L. Besides these indels, 227 single nucleotide variations (SNVs) were identified. We further investigated the variants that affected CDSs, and compared them to reported virulence determinants. Notably, almost all of the reported virulence determinants are included in these variants affected CDSs. In addition to variations previously described in mycoplasma adhesins (P97, P102, P146, P159, P216, and LppT), cell envelope proteins (P95), cell surface antigens (P36), secreted proteins and chaperone protein (DnaK), mutations in genes related to metabolism and growth may also contribute to the attenuated virulence in 168-L. Furthermore, many mutations were located in the previously described repeat motif, which may be of primary importance for virulence.
  
  
  CONCLUSIONS
  We studied the virulence attenuation mechanism of M. hyopneumoniae by comparative genomic analysis of virulent strain 168 and its attenuated high-passage strain 168-L. Our findings provide a preliminary survey of CDSs that may be related to virulence. While these include reported virulence-related genes, other novel virulence determinants were also detected. This new information will form the foundation of future investigations into the pathogenesis of M. hyopneumoniae and facilitate the design of new vaccines.
authors: Division of Animal Infectious Diseases, State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.
authors: Wei
authors: W
authors: Liu
authors: Shaobo
authors: S
authors: Xiao
authors: Mao
authors: M
authors: Li
authors: Shaohua
authors: S
authors: Guo
authors: Sha
authors: S
authors: Li
authors: Rui
authors: R
authors: Luo
authors: Zhixin
authors: Z
authors: Feng
authors: Bin
authors: B
authors: Li
authors: Zhemin
authors: Z
authors: Zhou
authors: Guoqing
authors: G
authors: Shao
authors: Huanchun
authors: H
authors: Chen
authors: Liurong
authors: L
authors: Fang
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics; D000818:Animals; D000954:Antigens, Surface / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D055028:Comparative Genomic Hybridization; D016680:Genome, Bacterial; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D045705:Mycoplasma hyopneumoniae / Q000235:genetics*; D016366:Open Reading Frames / Q000235:genetics; D045729:Pneumonia of Swine, Mycoplasmal / Q000382:microbiology; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D013552:Swine; D014774:Virulence / Q000235:genetics
chemical_list: D018829:Adhesins, Bacterial; D000954:Antigens, Surface; D001426:Bacterial Proteins; D018840:HSP70 Heat-Shock Proteins
references: J Bacteriol. 2004 Nov;186(21):7123-33
references: 15489423
references: Nucleic Acids Res. 1997 Mar 1;25(5):955-64
references: 9023104
references: J Microbiol Methods. 2006 Aug;66(2):263-75
references: 16458375
references: J Bacteriol. 2002 Dec;184(24):6929-41
references: 12446643
references: J Gen Microbiol. 1993 Feb;139(2):317-23
references: 7679720
references: Isr J Med Sci. 1987 Jun;23(6):657-62
references: 3667233
references: Infect Immun. 2008 Feb;76(2):658-63
references: 18070898
references: Infect Immun. 1994 May;62(5):1616-22
references: 8168922
references: Bioinformatics. 2009 Jul 15;25(14):1754-60
references: 19451168
references: Biochemistry (Mosc). 2009 Feb;74(2):215-20
references: 19267678
references: Infect Immun. 2005 Nov;73(11):7784-7
references: 16239586
references: Nucleic Acids Res. 2000 Jan 1;28(1):15-8
references: 10592170
references: J Bacteriol. 2005 Aug;187(16):5568-77
references: 16077101
references: Bioinformatics. 2007 Mar 15;23(6):673-9
references: 17237039
references: Vet Microbiol. 2008 Jan 25;126(4):297-309
references: 17964089
references: Biochem Mol Biol Int. 1997 Apr;41(4):821-31
references: 9111943
references: Genomics. 1997 Nov 15;46(1):24-36
references: 9403055
references: Microbiology (Reading). 2003 Jan;149(Pt 1):185-93
references: 12576592
references: Infect Immun. 1985 Aug;49(2):329-35
references: 2410363
references: Infect Immun. 1991 Apr;59(4):1217-22
references: 2004806
references: Microbiol Mol Biol Rev. 1998 Dec;62(4):1094-156
references: 9841667
references: Mol Microbiol. 2009 Feb;71(3):566-82
references: 19040640
references: Mol Microbiol. 2006 May;60(3):669-86
references: 16629669
references: Microb Pathog. 1994 Nov;17(5):313-22
references: 7723658
references: Proc Natl Acad Sci U S A. 1988 Apr;85(8):2444-8
references: 3162770
references: Cell Microbiol. 2012 Jan;14(1):81-94
references: 21951786
references: Am J Vet Res. 1993 Aug;54(8):1262-9
references: 8214893
references: PLoS One. 2008 Jun 11;3(6):e2375
references: 18584054
references: J Bacteriol. 2011 Feb;193(4):1016-7
references: 21148737
references: Infect Immun. 1990 Aug;58(8):2637-43
references: 1695206
references: J Bacteriol. 2007 Nov;189(22):7977-82
references: 17873054
references: Nucleic Acids Res. 1994 Sep;22(17):3445-9
references: 7937043
references: Vaccine. 2012 Mar 9;30(12):2153-8
references: 22266290
references: Science. 1997 Oct 24;278(5338):631-7
references: 9381173
references: Proteome Sci. 2009 Dec 21;7:45
references: 20025764
references: Protein Sci. 2002 Apr;11(4):980-5
references: 11910041
references: J Clin Microbiol. 1995 Mar;33(3):680-3
references: 7751376
references: Nucleic Acids Res. 1999 Jan 1;27(1):49-54
references: 9847139
references: Infect Immun. 2010 Apr;78(4):1760-71
references: 20123709
references: Bioinformatics. 2005 Aug 15;21(16):3422-3
references: 15976072
references: Mol Microbiol. 2003 Sep;49(5):1253-66
references: 12940985
references: Mol Cell Probes. 1991 Dec;5(6):451-7
references: 1723490
references: Vet Microbiol. 2007 Mar 31;121(1-2):83-93
references: 17182197
references: Genome Res. 2004 Jul;14(7):1394-403
references: 15231754
references: Infect Immun. 1985 May;48(2):576-8
references: 3988348
references: Am J Vet Res. 1990 Mar;51(3):339-43
references: 2316909
references: FASEB J. 2000 Feb;14(2):231-41
references: 10657980
references: Infect Immun. 1995 Mar;63(3):1013-9
references: 7868222
references: Infect Immun. 2000 May;68(5):3056-60
references: 10769015
references: Microbiology (Reading). 2006 Apr;152(Pt 4):937-944
references: 16549658
references: Clin Diagn Lab Immunol. 2003 May;10(3):459-68
references: 12738649
references: Trends Microbiol. 2003 Nov;11(11):527-35
references: 14607070
references: Infect Immun. 2006 Jan;74(1):481-7
references: 16369004
references: Clin Diagn Lab Immunol. 2000 Jul;7(4):528-35
references: 10882646
references: Infect Immun. 1994 Oct;62(10):4367-73
references: 7927697
references: Vet Microbiol. 2006 Sep 10;116(4):258-69
references: 16730926
references: Bioinformatics. 2000 Oct;16(10):944-5
references: 11120685
references: J Bacteriol. 2004 Sep;186(17):5790-8
references: 15317784
references: J Proteome Res. 2012 Mar 2;11(3):1924-36
references: 22229926
references: J Mol Biol. 1990 Oct 5;215(3):403-10
references: 2231712
references: Protein Sci. 2004 May;13(5):1422-5
references: 15075401