Application of Genomics to Understand the Pathogenic Microbial Diversity

  • Jhasketan Badhai
  • Sushanta Deb
  • Subrata K. DasEmail author


Conventional bacteriological, biochemical, and molecular methods used in diagnostic laboratories for identification of pathogens are laborious, time-consuming, and expensive. Moreover, it provides limited information which is not sufficient to evaluate the disease outbreak and epidemiological investigations. Due to drastic reduction in sequencing cost concomitant with an increase in the sequence quality, whole genome sequencing of prokaryotes based on NGS is economically feasible as a routine tool for clinical diagnostics and surveillance of pathogens. Availability of comprehensive biological information databases and advanced bioinformatics tools for analysis of pan-genomes, single nucleotide polymorphisms, virulence factors, antibiotic resistance, recombination, and lateral or horizontal gene transfer events have greatly facilitated the identification of emerging pathogenic strains, understanding their population dynamics, genomic plasticity, virulence and pathogenicity, and epidemiology. Genomics studies have greatly enriched our knowledge of various genetic events that have shaped pathogenic bacterial genomes and guided their evolution, such as mutations, insertions, deletions, duplications, inversions, transpositions, and recombination. Whole genome analyses of the classical mammalian Bordetella spp., Vibrio cholerae, and Salmonella enterica have revealed important features of their virulence and pathogenicity, as well as their evolution as successful human pathogens. Gene inactivation, polymorphism, accumulation of IS elements, and genome decay have guided the evolution of the classical Bordetella spp. as separate host-restricted pathogens, while the acquisition of pathogenicity islands by HGT mechanisms has the greatest impact on the evolution, virulence, and pathogenicity of Vibrio cholerae and Salmonella enterica.


Genomics Pan-genome SNPs Virulence factors Antibiotic resistance Pathogenicity Recombination Horizontal gene transfer PAIs Bordetella Vibrio Salmonella 


  1. Abe A, Nagamatsu K, Watanabe M (2008) The Bordetella type III secretion system: Its application to vaccine development. Microbiol Immunol 52:128–133PubMedCrossRefPubMedCentralGoogle Scholar
  2. Akerley BJ, Monack DM, Falkow S, Miller JF (1992) The bvgAS locus negatively controls motility and synthesis of flagella in Bordetella bronchiseptica. J Bacteriol 174:980–990PubMedPubMedCentralCrossRefGoogle Scholar
  3. Alikhan NF, Petty NK, Ben Zakour NL, Beatson SA (2011) BLAST Ring Image Generator (BRIG): Simple prokaryote genome comparisons. BMC Genomics 12:402PubMedPubMedCentralCrossRefGoogle Scholar
  4. Altschul S, Gish W, Miller W, Myers E, Lipman D (1990) Basic local alignment search tool. J Mol Biol 215:403–410CrossRefPubMedGoogle Scholar
  5. Altschul AF, Madden TL, Schaffer AA, Zhang J, Zhang Z et al (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25:3389–3402PubMedPubMedCentralCrossRefGoogle Scholar
  6. Aujoulat F, Roger F, Bourdier A, Lotthé A, Lamy B et al (2012) From environment to man: genome evolution and adaptation of human opportunistic bacterial pathogens. Genes 3:191–232PubMedPubMedCentralCrossRefGoogle Scholar
  7. Ausiello CM, Cassone A (2014) Acellular pertussis vaccines and pertussis resurgence: revise or replace? mBio 5:e01339–e01314PubMedPubMedCentralCrossRefGoogle Scholar
  8. Aziz RK, Bartels D, Best A, DeJongh M, Disz T et al (2008) The RAST Server: rapid annotations using subsystems technology. BMC Genomics 9:1–15CrossRefGoogle Scholar
  9. Badhai J, Das SK (2016) Characterization of three novel SXT/R391 integrating conjugative elements ICEMfuInd1a and ICEMfuInd1b, and ICEMprChn1 identified in the genomes of Marinomonas fungiae JCM 18476T and Marinomonas profundimaris strain D104. Front Microbiol 7:1896PubMedPubMedCentralGoogle Scholar
  10. Barrick JE, Yu DS, Yoon SH, Jeong H, Oh TK et al (2009) Genome evolution and adaptation in a long-term experiment with Escherichia coli. Nature 461:1243–1247PubMedCrossRefPubMedCentralGoogle Scholar
  11. Bi D, Xu Z, Harrison E, Tai C, Wei Y et al (2012) ICEberg: a web- based resource for integrative and conjugative elements found in Bacteria. Nucleic Acids Res 40:D621–D626PubMedCrossRefPubMedCentralGoogle Scholar
  12. Blanc-Potard AB, Solomon F, Kayser J, Groisman EA (1999) The SPI-3 pathogenicity island of Salmonella enterica. J Bacteriol 181:998–1004PubMedPubMedCentralGoogle Scholar
  13. Bouchez V, Guiso N (2015) Bordetella pertussis, B. parapertussis, vaccines and cycles of whooping cough. Pathog Dis 73:1–6CrossRefGoogle Scholar
  14. Brinig MM, Register KB, Ackermann MR, Relman DA (2006) Genomic features of Bordetella parapertussis clades with distinct host species specificity. Genome Biol 7:R81PubMedPubMedCentralCrossRefGoogle Scholar
  15. Bryant J, Chewapreecha C, Bentley SD (2012) Developing insights into the mechanisms of evolution of bacterial pathogens from whole-genome sequences. Future Microbiol 7:1283–1296PubMedPubMedCentralCrossRefGoogle Scholar
  16. Canchaya C, Proux C, Fournous G, Bruttin A, Brussow H (2003) Prophage genomics. Microbiol Mol Biol Rev 67:238–276PubMedPubMedCentralCrossRefGoogle Scholar
  17. Carattoli A, Zankari E, García-Fernández A, Voldby Larsen M, Lund O et al (2014) In silico detection and typing of plasmids using PlasmidFinder and plasmid multilocus sequence typing. Antimicrob Agents Chemother 58:3895–3903PubMedPubMedCentralCrossRefGoogle Scholar
  18. Carraro N, Burrus V (2014) Biology of three ICE families: SXT/R391, ICEBs1, and ICESt1/ICESt3. Microbiol Spectr 2:1–20Google Scholar
  19. Carver TJ, Rutherford KM, Berriman M, Rajandream MA, Barrell BG et al (2005) ACT: the artemis comparison tool. Bioinformatics 21:3422–3423PubMedCrossRefPubMedCentralGoogle Scholar
  20. Carver TJ, Berriman M, Tivey A, Patel C, Böhme U et al (2008) Artemis and ACT: viewing, annotating and comparing sequences stored in a relational database. Bioinformatics 24:2672–2676PubMedPubMedCentralCrossRefGoogle Scholar
  21. Champion GA, Neely MN, Brennan MA, DiRita VJ (1997) A branch in the ToxR regulatory cascade of Vibrio cholerae revealed by characterization of toxT mutant strains. Mol Microbiol 23:323–331PubMedCrossRefPubMedCentralGoogle Scholar
  22. Chawley P, Samal HB, Prava J, Suar M, Mahapatra RK (2014) Comparative genomics study for identification of drug and vaccine targets in Vibrio cholerae: MurA ligase as a case study. Genomics 103:83–93PubMedCrossRefPubMedCentralGoogle Scholar
  23. Che D, Hasan MS, Chen B (2014a) Identifying pathogenicity islands in bacterial pathogenomics using computational approaches. Pathogens 3:36–56PubMedPubMedCentralCrossRefGoogle Scholar
  24. Che D, Wang H, Fazekas J, Chen B (2014b) An accurate genomic island prediction method for sequenced bacterial and archaeal genomes. J Proteomics Bioinformatics 7:214–221Google Scholar
  25. Chen L, Zheng D, Liu B, Yang J, Jin Q (2016) VFDB 2016: hierarchical and refined dataset for bigdata analysis-10 years on. Nucleic Acids Res 44:D694–D697PubMedCrossRefPubMedCentralGoogle Scholar
  26. Cherry JD, Heininger U (2014) Pertussis and other bordetella infections. In: Feigin RD, Cherry JD, Harrison GJ et al (eds) Textbook of pediatric infectious diseases, 7th edn. WB Saunders, Philadelphia, pp 1616–1639Google Scholar
  27. Chiapello H, Gendrault A, Caron C, Blum J, Petit MA et al (2008) MOSAIC: an online database dedicated to the comparative genomics of bacterial strains at the intra-species level. BMC Bioinf 9:498CrossRefGoogle Scholar
  28. Chiu CH, Tang P, Chu C, Hu S, Bao Q et al (2005) The genome sequence of Salmonella enterica serovar Choleraesuis, a highly invasive and resistant zoonotic pathogen. Nucleic Acids Res 33:1690–1698PubMedPubMedCentralCrossRefGoogle Scholar
  29. Chun J, Grim CJ, Hasan NA, Lee JH, Choi SY et al (2009) Comparative genomics reveals mechanism for short-term and long-term clonal transitions in pandemic Vibrio cholerae. Proc Natl Acad Sci USA 106:15442–15447PubMedCrossRefPubMedCentralGoogle Scholar
  30. Cotter PA, Jones AM (2003) Phosphorelay control of virulence gene expression in Bordetella. Trends Microbiol 11:367–373PubMedCrossRefPubMedCentralGoogle Scholar
  31. Crofts TS, Gasparrini AJ, Dantas G (2017) Next-generation approaches to understand and combat the antibiotic resistome. Nat Rev Microbiol 15:422–434PubMedPubMedCentralCrossRefGoogle Scholar
  32. Cummings CA, Brinig MM, Lepp PW, van de Pas S, Relman DA (2004) Bordetella species are distinguished by patterns of substantial gene loss and host adaptation. J Bacteriol 186:1484–1492PubMedPubMedCentralCrossRefGoogle Scholar
  33. Cummings CA, Bootsma HJ, Relman DA, Miller JF (2006) Species- and strain-specific control of a complex, flexible regulon by Bordetella BvgAS. J Bacteriol 188:1775–1785PubMedPubMedCentralCrossRefGoogle Scholar
  34. D’Costa VM, King CE, Kalan L, Morar M, Sung WWL et al (2011) Antibiotic resistance is ancient. Nature 477:457–461PubMedCrossRefPubMedCentralGoogle Scholar
  35. Darling AE, Mau B, Perna NT (2010) progressiveMauve: multiple genome alignment with gene gain, loss and rearrangement. PLoS One 5:e11147PubMedPubMedCentralCrossRefGoogle Scholar
  36. Deiwick J, Nikolaus T, Erdogan S, Hensel M (1999) Environmental regulation of Salmonella pathogenicity island 2 gene expression. Mol Microbiol 31:1759–1773PubMedCrossRefPubMedCentralGoogle Scholar
  37. Deneke C, Rentzsch R, Renard BY (2017) PaPrBaG: A machine learning approach for the detection of novel pathogens from NGS data. Sci Rep 7:39194PubMedPubMedCentralCrossRefGoogle Scholar
  38. Diavatopoulos DA, Cummings CA, Schouls LM, Brinig MM, Relman DA et al (2005) Bordetella pertussis, the causative agent of whooping cough, evolved from a distinct, human-associated lineage of B. bronchiseptica. PLoS Pathog e45:1Google Scholar
  39. Donkor ES (2013) Sequencing of bacterial genomes: principles and insights into pathogenesis and development of antibiotics. Genes 4:556–572PubMedPubMedCentralCrossRefGoogle Scholar
  40. Dziejman M, Balon E, Boyd D, Fraser CM, Heidelberg JF et al (2002) Comparative genomic analysis of Vibrio cholerae: genes that correlate with cholera endemic and pandemic disease. Proc Natl Acad Sci USA 99:1556–1561PubMedCrossRefPubMedCentralGoogle Scholar
  41. Entrez Sequences Help [Internet] (2010). National Center for Biotechnology Information (US), Bethesda. Available at:
  42. Faruque SM, Mekalanos JJ (2003) Pathogenicity islands and phages in Vibrio cholerae evolution. Trends Microbiol 11:505–510PubMedCrossRefPubMedCentralGoogle Scholar
  43. Faruque SM, Alber MJ, Mekalanos JJ (1998) Epidemiology, genetics, and ecology of toxigenic Vibrio cholerae. Microbiol Mol Biol Rev 62:1301–1314PubMedPubMedCentralGoogle Scholar
  44. Faruque SM, Sack DA, Sack RB, Colwell RR, Takeda Y et al (2003) Emergence and evolution of Vibrio cholerae O139. Proc Natl Acad Sci USA 100:1304–1309PubMedCrossRefPubMedCentralGoogle Scholar
  45. Faruque SM, Nair GB, Mekalanos JJ (2004) Genetics of stress adaptation and virulence in toxigenic Vibrio cholerae. DNA Cell Biol 23:723–741PubMedCrossRefPubMedCentralGoogle Scholar
  46. Fasano A, Baudry B, Pumplin DW, Wasserman SS, Tall BD et al (1991) Vibrio cholerae produces a second enterotoxin, which affects intestinal tight junctions. Proc Natl Acad Sci USA 88:5242–5246PubMedCrossRefPubMedCentralGoogle Scholar
  47. Finn RD, Clements J, Eddy SR (2011) HMMER web server: interactive sequence similarity searching. Nucleic Acids Res 39:W29–W37PubMedPubMedCentralCrossRefGoogle Scholar
  48. Finn RD, Bateman A, Clements J, Coggill P, Eberhardt RY et al (2014) Pfam: The protein families’ database. Nucleic Acids Res 42:222–230CrossRefGoogle Scholar
  49. Folkesson A, Lofdahl S, Normark S (2002) The Salmonella enterica subspecies I specific centisome 7 genomic island encodes novel protein families present in bacteria living in close contact with eukaryotic cells. Res Microbiol 153:537–545PubMedCrossRefPubMedCentralGoogle Scholar
  50. Forde BM, O’Toole PW (2013) Next-generation sequencing technologies and their impact on microbial genomics. Brief Funct Genomics 12:440–453PubMedCrossRefPubMedCentralGoogle Scholar
  51. Fookes M, Schroeder GN, Langridge GC, Blondel CJ et al (2011) Salmonella bongori provides insights into the evolution of the Salmonellae. PLoS Pathog e1002191:7Google Scholar
  52. Forsberg KJ, Reyes A, Wang B, Selleck EM, Sommer MOA et al (2012) The shared antibiotic resistome of soil bacteria and human pathogens. Science 337:1107–1111PubMedPubMedCentralCrossRefGoogle Scholar
  53. Fouts DE, Brinkac L, Beck E, Inman J, Sutton G (2012) PanOCT: automated clustering of orthologs using conserved gene neighborhood for pan-genomic analysis of bacterial strains and closely related species. Nucleic Acids Res 40:e172PubMedPubMedCentralCrossRefGoogle Scholar
  54. Fuentes JA, Villagra N, Castillo-Ruiz M, Mora GC (2008) The Salmonella Typhi hlyE gene plays a role in invasion of cultured epithelial cells and its functional transfer to S. typhimurium promotes deep organ infection in mice. Res Microbiol 159:279–287PubMedCrossRefPubMedCentralGoogle Scholar
  55. Fullner KJ, Mekalanos JJ (1999) Genetic characterization of a new type IV-A pilus gene cluster found in both classical and El Tor biotypes of Vibrio cholerae. Infect Immun 67:1393–1404PubMedPubMedCentralGoogle Scholar
  56. Gardner SN, Hall BG (2013) When whole-genome alignments just won’t work: Ksnp V2 Software for alignment–free Snp discovery and phylogenetics of hundreds of microbial genomes. PLoS One 8:e81760PubMedPubMedCentralCrossRefGoogle Scholar
  57. Gardner SN, Slezak T, Hall BG (2015) kSNP3.0: SNP detection and phylogenetic analysis of genomes without genome alignment or reference genome. Bioinformatics 31:2877–2878PubMedCrossRefPubMedCentralGoogle Scholar
  58. Garg A, Gupta D (2008) VirulentPred: a SVM based prediction method for virulent proteins in bacterial pathogens. BMC Bioinf 9:62CrossRefGoogle Scholar
  59. Garmendia J, Beuzon CR, Ruiz-Albert J, Holden DW (2003) The roles of SsrA-SsrB and OmpR-EnvZ in the regulation of genes encoding the Salmonella typhimurium SPI-2 type III secretion system. Microbiology 149:2385–2396PubMedCrossRefPubMedCentralGoogle Scholar
  60. Georgiades K, Raoult D (2011) Comparative genomics evidence that only protein toxins are tagging bad bugs. Front Cell Infect Microbiol 1:7PubMedPubMedCentralGoogle Scholar
  61. Gilchrist CA, Turner SD, Riley MF, Petri WA, Hewlett EL (2015) Whole-genome sequencing in outbreak analysis. Clin Microbiol Rev 28:541–563PubMedPubMedCentralCrossRefGoogle Scholar
  62. Goldberg MB, Boyko SA, Calderwood SB (1991) Positive transcriptional regulation of an iron-regulated virulence gene in Vibrio cholerae. Proc Natl Acad Sci USA 88:1125–1129PubMedCrossRefPubMedCentralGoogle Scholar
  63. Gu J, Wang Y, Lilburn T (2009) A comparative genomics, network-based approach to understanding virulence in Vibrio cholerae. J Bacteriol 191:6262–6272PubMedPubMedCentralCrossRefGoogle Scholar
  64. Gunn JS, Alpuche-Aranda CM, Loomis WP, Belden WJ et al (1995) Characterization of the Salmonella typhimurium pagC/pagD chromosomal region. J Bacteriol 177:5040–5047PubMedPubMedCentralCrossRefGoogle Scholar
  65. Gupta SK, Padmanabhan BR, Diene SM, Lopez-Rojas R, Kempf M et al (2014) ARG-ANNOT, a new bioinformatic tool to discover antibiotic resistance genes in bacterial genomes. Antimicrob Agents Chemother 58:212e20Google Scholar
  66. Hacker J, Kaper JB (2000) Pathogenicity islands and the evolution of microbes. Annu Rev Microbiol 54:641–679PubMedCrossRefPubMedCentralGoogle Scholar
  67. Hacker J, Blum-Oehler G, Muhldorfer I, Tschape H (1997) Pathogenicity islands of virulent bacteria: structure, function and impact on microbial evolution. Mol Microbiol 23:1089–1097PubMedCrossRefPubMedCentralGoogle Scholar
  68. Haneda T, Ishii Y, Danbara H, Okada N (2009) Genome-wide identification of novel genomic islands that contribute to Salmonella virulence in mouse systemic infection. FEMS Microbiol Lett 297:241–249PubMedCrossRefPubMedCentralGoogle Scholar
  69. Hansen-Wester I, Hensel M (2002) Genome-based identification of chromosomal regions specific for Salmonella spp. Infect Immun 70:2351–2360PubMedPubMedCentralCrossRefGoogle Scholar
  70. Harrison E, Brockhurst MA (2012) Plasmid-mediated horizontal gene transfer is a coevolutionary process. Trends Microbiol 20:262–267PubMedCrossRefPubMedCentralGoogle Scholar
  71. Hegerle N, Rayat L, Dore G, Zidane N, Bedouelle H et al (2013) In vitro and in vivo analysis of the expression of the Bordetella type three secretion system effector A in Bordetella bronchiseptica, Bordetella pertussis and Bordetella parapertussis. Microbes Infect 15:399–408PubMedCrossRefPubMedCentralGoogle Scholar
  72. Heidelberg JF, Eisen JA, Nelson WC, Clayton RA, Gwinn ML et al (2000) DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae. Nature 406:477–483PubMedCrossRefPubMedCentralGoogle Scholar
  73. Hendrix RW, Lawrence JG, Hatfull GF, Casjens S (2000) The origins and ongoing evolution of viruses. Trends Microbiol 8:504–508PubMedCrossRefPubMedCentralGoogle Scholar
  74. Hensel M (2004) Evolution of pathogenicity islands of Salmonella enterica. Int J Med Microbiol 294:95–102PubMedCrossRefPubMedCentralGoogle Scholar
  75. Herrou J, Debrie AS, Willery E, Renaud-Mongénie G, Locht C et al (2009) Molecular evolution of the two-component system BvgAS involved in virulence regulation in Bordetella. PLoS One 4:10PubMedCentralCrossRefGoogle Scholar
  76. Hibberd ML (2013) Microbial genomics: an increasingly revealing interface in human health and disease. Genome Med 5:10–12CrossRefGoogle Scholar
  77. Hsiao WW, Ung K, Aeschliman D, Bryan J, Finlay BB et al (2005) Evidence of a large novel gene pool associated with prokaryotic genomic islands. PLoS Genetics 1:e62PubMedPubMedCentralCrossRefGoogle Scholar
  78. Jacob-Dubuisson F, Locht C (2007) The Bordetella adhesins. Bordetella: molecular microbiology. Horizon Biosci:69–96Google Scholar
  79. Johnson CM, Grossman AD (2015) Integrative and conjugative elements (ICEs): what they do and how they work. Annu Rev Genet 49:577–601PubMedPubMedCentralCrossRefGoogle Scholar
  80. Kanehisa M, Goto S (2000) KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res 28:27–30PubMedPubMedCentralCrossRefGoogle Scholar
  81. Karaolis DK, Johnson JA, Bailey CC, Boedeker EC, Kaper JB et al (1998) A Vibrio cholerae pathogenicity island associated with epidemic and pandemic strains. Proc Natl Acad Sci USA 95:3134–3139PubMedCrossRefPubMedCentralGoogle Scholar
  82. Kilgore PE, Salim AM, Zervos MJ, Schmitt H (2016) Pertussis: microbiology, disease, treatment, and prevention. Clin Microbiol Rev 29:449–486PubMedPubMedCentralCrossRefGoogle Scholar
  83. Klein NP, Bartlett J, Fireman B, Aukes L, Buck PO et al (2017) Waning protection following 5 doses of a 3-component diphtheria, tetanus, and acellular pertussis vaccine. Vaccine 35:3395–3400PubMedCrossRefPubMedCentralGoogle Scholar
  84. Korves T, Colosimo ME (2009) Controlled vocabularies for microbial virulence factors. Trends Microbiol 17:279–285PubMedCrossRefPubMedCentralGoogle Scholar
  85. Kurushima J, Kuwae A, Abe A (2012) Btc22 chaperone is required for secretion and stability of the type III secreted protein Bsp22 in Bordetella bronchiseptica. FEMS Microbiol Lett 331:144–151PubMedCrossRefPubMedCentralGoogle Scholar
  86. Laing C, Buchanan C, Taboada EN, Zhang Y, Kropinski A et al (2010) Pan-genome sequence analysis using Panseq: an online tool for the rapid analysis of core and accessory genomic regions. BMC Bioinf 11:461CrossRefGoogle Scholar
  87. Land M, Hauser L, Jun SR, Nookaew I, Leuze MR et al (2015) Insights from 20 years of bacterial genome sequencing. Funct Integr Genomics 15:141–161PubMedPubMedCentralCrossRefGoogle Scholar
  88. Langille MG, Hsiao WW, Brinkman FS (2010) Detecting genomic islands using bioinformatics approaches. Nat Rev Microbiol 8:373–382PubMedCrossRefPubMedCentralGoogle Scholar
  89. Lasken RS, McLean JS (2014) Recent advances in genomic DNA sequencing of microbial species from single cells. Nat Rev Genetics 15:577–584PubMedCrossRefPubMedCentralGoogle Scholar
  90. Lawrence JG, Hendrickson H (2005) Genome evolution in bacteria: order beneath chaos. Curr Opin Microbiol 8:572–578PubMedCrossRefPubMedCentralGoogle Scholar
  91. Lin W, Fullner KJ, Clayton R, Sexton JA, Rogers MB et al (1999) Identification of a vibrio cholerae RTX toxin gene cluster that is tightly linked to the cholera toxin prophage. Proc Natl Acad Sci USA 96:1071–1076PubMedCrossRefPubMedCentralGoogle Scholar
  92. Linz B, Ivanov YV, Preston A, Brinkac L, Parkhill J et al (2016) Acquisition and loss of virulence-associated factors during genome evolution and speciation in three clades of Bordetella species. BMC Genomics 17:767PubMedPubMedCentralCrossRefGoogle Scholar
  93. Liu B, Pop M (2009) ARDB – Antibiotic Resistance Genes Database. Nucleic Acids Res 37:D443–D447PubMedCrossRefPubMedCentralGoogle Scholar
  94. Maiden MC, Bygraves JA, Feil E, Morelli G, Russell JE et al (1998) Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms. Proc Natl Acad Sci USA 95:3140–3145PubMedCrossRefPubMedCentralGoogle Scholar
  95. Marcus SL, Brumell JH, Pfeifer CG, Finlay BB (2000) Salmonella pathogenicity islands: big virulence in small packages. Microbes Infect 2:145–156PubMedCrossRefPubMedCentralGoogle Scholar
  96. Markowitz VM, Chen IMA, Palaniappan K, Chu K, Szeto E et al (2012) IMG: The integrated microbial genomes database and comparative analysis system. Nucleic Acids Res 40:115–122CrossRefGoogle Scholar
  97. Mattoo S, Cherry JD (2005) Molecular pathogenesis, epidemiology, and clinical manifestations of respiratory infections due to Bordetella pertussis and other Bordetella subspecies. Clin Microbiol Rev 18:326–382PubMedPubMedCentralCrossRefGoogle Scholar
  98. Mazel D, Dychinco B, Webb VA, Davies J (1998) A distinctive class of integron in the Vibrio cholerae genome. Science 280:605–608PubMedCrossRefPubMedCentralGoogle Scholar
  99. Mazumder R, Natale DA, Murthy S, Thiagarajan R, Wu CH (2005) Computational identification of strain-, species- and genus-specific proteins. BMC Bioinf 6:1–9CrossRefGoogle Scholar
  100. McArthur AG, Waglechner N, Nizam F, Yan A, Azad MA et al (2013) The comprehensive antibiotic resistance database. Antimicrob Agents Chemother 57:3348e57CrossRefGoogle Scholar
  101. McClelland M, Sanderson KE, Spieth J, Clifton SW et al (2001) Complete genome sequence of Salmonella enterica serovar Typhimurium LT2. Nature 413:852–856PubMedCrossRefPubMedCentralGoogle Scholar
  102. McCutcheon JP, Moran NA (2012) Extreme genome reduction in symbiotic bacteria. Nat Rev Microbiol 10:13–26CrossRefGoogle Scholar
  103. McGann P, Bunin JL, Snesrud E, Singh S, Maybank R et al (2016) Real time application of whole genome sequencing for outbreak investigation – What is an achievable turnaround time? Diagn Microbiol Infect Dis 85:277–282PubMedCrossRefPubMedCentralGoogle Scholar
  104. Melvin JA, Scheller EV, Miller JF, Cotter PA (2014) Bordetella pertussis pathogenesis: Current and future challenges. Nat Rev Microbiol 12:274–288PubMedPubMedCentralCrossRefGoogle Scholar
  105. Merhej V, Royer-Carenzi M, Pontarotti P, Raoult D (2009) Massive comparative genomic analysis reveals convergent evolution of specialized bacteria. Biol Direct 4:1–25CrossRefGoogle Scholar
  106. Merhej V, Georgiades K, Raoult D (2013) Postgenomic analysis of bacterial pathogens repertoire reveals genome reduction rather than virulence factors. Brief Funct Genomics 12:291–304PubMedCrossRefPubMedCentralGoogle Scholar
  107. Miller SI, Kukral AM, Mekalanos JJ (1989) A two-component regulatory system (phoP phoQ) controls Salmonella typhimurium virulence. Proc Natl Acad Sci USA 86:5054–5058PubMedCrossRefPubMedCentralGoogle Scholar
  108. Moon K, Bonocora RP, Kim DD, Chen Q, Wade JT et al (2017) The BvgAS regulon of Bordetella pertussis. mBio 8:1–15CrossRefGoogle Scholar
  109. Moran NA (2002) Microbial minimalism: genome reduction in bacterial pathogens. Cell 108:583–586PubMedCrossRefPubMedCentralGoogle Scholar
  110. Morris CE, Bardin M, Berge O, Frey-Klett P, Fromin N et al (2002) Microbial biodiversity: approaches to experimental design and hypothesis testing in primary scientific literature from 1975 to 1999. Microbiol Mol Biol Rev 66:592–616PubMedPubMedCentralCrossRefGoogle Scholar
  111. Nakamura Y, Itoh T, Matsuda H, Gojobori T (2004) Biased biological functions of horizontally transferred genes in prokaryotic genomes. Nat Genet 36:760–766PubMedCrossRefPubMedCentralGoogle Scholar
  112. Narihiro T, Kamagata Y (2017) Genomics and Metagenomics in microbial ecology: recent advances and challenges. Microbes Environ 32:1–4PubMedPubMedCentralCrossRefGoogle Scholar
  113. Nesme J, Ce’cillon S, Delmont TO, Monier JM, Vogel TM et al (2014) Large-scale metagenomic-based study of antibiotic resistance in the environment. Curr Biol 24:1096–1100PubMedCrossRefPubMedCentralGoogle Scholar
  114. Nicholson TL (2007) Construction and validation of a first-generation Bordetella bronchiseptica long-oligonucleotide microarray by transcriptional profiling the Bvg regulon. BMC Genomics 8:220PubMedPubMedCentralCrossRefGoogle Scholar
  115. Ochman H, Davalos LM (2006) The nature and dynamics of bacterial genomes. Science 311:1730–1733PubMedCrossRefPubMedCentralGoogle Scholar
  116. Olaitan AO, Rolain JM (2016) Ancient resistome. MicrobiologySpectrum 4: PoH-0008-2015Google Scholar
  117. Ou HY, He X, Harrison EM, Kulasekara BR, Thani AB et al (2007) MobilomeFINDER: web-based tools for in silico and experimental discovery of bacterial genomic islands. Nucleic Acids Res 35:W97–W104PubMedPubMedCentralCrossRefGoogle Scholar
  118. Overbeek R, Begley T, Butler RM, Choudhuri JV, Chuang HY et al (2005) The subsystems approach to genome annotation and its use in the project to annotate 1000 genomes. Nucleic Acids Res 33:5691–5702PubMedPubMedCentralCrossRefGoogle Scholar
  119. Overbeek R, Olson R, Pusch GD, Olsen GJ, Davis JJ et al (2014) The SEED and the rapid annotation of microbial genomes using subsystems technology (RAST). Nucleic Acids Res 42:206–214CrossRefGoogle Scholar
  120. Pallen MJ, Wren BW (2007) Bacterial pathogenomics. Nature 449:835–842PubMedCrossRefPubMedCentralGoogle Scholar
  121. Park J, Zhang Y, Buboltz AM, Zhang X, Schuster SC et al (2012) Comparative genomics of the classical Bordetella subspecies: the evolution and exchange of virulence-associated diversity amongst closely related pathogens. BMC Genomics 13:545PubMedPubMedCentralCrossRefGoogle Scholar
  122. Parkhill J, Dougan G, James KD, Thomson NR, Pickard D, Wain J et al (2001) Complete genome sequence of a multiple drug resistant Salmonella enterica serovar Typhi CT18. Nature 413:848–852PubMedCrossRefPubMedCentralGoogle Scholar
  123. Parkhill J, Sebaihia M, Preston A, Murphy LD, Thomson N et al (2003) Comparative analysis of the genome sequences of Bordetella pertussis, Bordetella parapertussis and Bordetella bronchiseptica. Nat Genet 35:32–40PubMedCrossRefPubMedCentralGoogle Scholar
  124. Perron GG, Lee AEG, Wang Y, Huang WE, Barraclough TG (2012) Bacterial recombination promotes the evolution of multi-drug-resistance in functionally diverse populations. Philos Trans R Soc B 279:1477–1484Google Scholar
  125. Peterson JW (1996) Bacterial pathogenesis. In: Baron S (ed) Medical microbiology, 4th edn. University of Texas Medical Branch, GalvestonGoogle Scholar
  126. Pickard D, Wain J, Baker S, Line A, Chohan S, Fookes M et al (2003) Composition, acquisition, and distribution of the Vi exopolysaccharide-encoding Salmonella enterica pathogenicity island SPI-7. J Bacteriol 185:5055–5065PubMedPubMedCentralCrossRefGoogle Scholar
  127. Pollitzer R (1959) History of the disease. In: Pollitzer R (ed) Cholera. World Health Organization, Geneva, pp 11–50Google Scholar
  128. Raskin DM, Seshadri R, Pukatzki SU, Mekalanos JJ (2006) Bacterial genomics and pathogen evolution. Cell 124:703–714PubMedCrossRefPubMedCentralGoogle Scholar
  129. Reen FJ, Boyd EF (2005) Molecular typing of epidemic and nonepidemic Vibrio cholerae isolates and differentiation of V. cholerae and V. mimicus isolates by PCR-single-strand conformation polymorphism analysis. J Appl Microbiol 98:544–555PubMedCrossRefPubMedCentralGoogle Scholar
  130. Rouli L, Merhej V, Fournier PE, Raoult D (2015) The bacterial pangenome as a new tool for analysing pathogenic bacteria. New Microbes New Infect 7:72–85PubMedPubMedCentralCrossRefGoogle Scholar
  131. Sabbagh SC, Forest CG, Lepage C, Leclerc JM, Daigle F (2010) So similar, yet so different: uncovering distinctive features in the genomes of Salmonella enterica serovars Typhimurium and Typhi. FEMS Microbiol Lett 305:1–13PubMedCrossRefPubMedCentralGoogle Scholar
  132. Saha S, Raghava GP (2006) VICMpred: an SVM-based method for the prediction of functional proteins of Gram-negative bacteria using amino acid patterns and composition. Genomics Proteomics Bioinformatics 4:42–47PubMedPubMedCentralCrossRefGoogle Scholar
  133. Shah DH, Lee MJ, Park JH, Lee JH, Eo SK, Kwon JT, Chae JS (2005) Identification of Salmonella gallinarum virulence genes in a chicken infection model using PCR-based signature-tagged mutagenesis. Microbiology 151:3957–3968PubMedCrossRefPubMedCentralGoogle Scholar
  134. Shimada T, Arakawa E, Itoh K, Okitsu T, Matsushima A, Asai Y, Yamai S, Nakazato T, Nair GB, Albert MJ, Takeda Y (1994) Extended serotyping scheme for Vibrio cholerae. Curr Microbiol 28:175–178CrossRefGoogle Scholar
  135. Siguier P, Perochon J, Lestrade L, Mahillon J, Chandler M (2006) ISfinder: the reference centre for bacterial insertion sequences. Nucleic Acids Res 34:D32–D36PubMedCrossRefPubMedCentralGoogle Scholar
  136. Socolovschi C, Audoly G, Raoult D (2013) Connection of toxin-antitoxin modules to inoculation eschar and arthropod vertical transmission in Rickettsiales. Comp Immunol Microbiol Infect Dis 36:199–209PubMedCrossRefPubMedCentralGoogle Scholar
  137. Soumana IH, Linz B, Harvill ET (2017) Environmental origin of the genus Bordetella. Front Microbiol 8:1–10Google Scholar
  138. Tatusov RL, Natale DA, Garkavtsev IV, Tatusova TA, Shankavaram UT et al (2001) The COG database: new developments in phylogenetic classification of proteins from complete genomes. Nucleic Acids Res 29:22–28PubMedPubMedCentralCrossRefGoogle Scholar
  139. Tatusova T, DiCuccio M, Badretdin A, Chetvernin V, Nawrocki EP et al (2016) NCBI prokaryotic genome annotation pipeline. Nucleic Acids Res 44:6614–6624PubMedPubMedCentralCrossRefGoogle Scholar
  140. Tettelin H, Masignani V, Cieslewicz MJ, Donati C, Medini D et al (2005) Genome analysis of multiple pathogenic isolates of Streptococcus agalactiae: implications for the microbial ‘pan-genome’. Proc Natl Acad Sci USA 102:13950–13955PubMedCrossRefPubMedCentralGoogle Scholar
  141. Tindall BJ, Grimont PA, Garrity GM, Euzeby JP (2005) Nomenclature and taxonomy of the genus Salmonella. Int J Syst Evol Microbiol 55:521–524PubMedCrossRefPubMedCentralGoogle Scholar
  142. Townsend SM, Kramer NE, Edwards R, Baker S, Hamlin N et al (2001) Salmonella enterica serovar Typhi possesses a unique repertoire of fimbrial gene sequences. Infect Immun 69:2894–2901PubMedPubMedCentralCrossRefGoogle Scholar
  143. Tsai CT, Huang WL, Ho SJ, Shu LS, Ho SY (2009) Virulent-GO: prediction of virulent proteins in bacterial pathogens utilizing gene ontology terms. Development 1:3Google Scholar
  144. UniProt Consortium (2012) Reorganizing the protein space at the Universal Protein Resource (UniProt). Nucleic Acids Res 40:D71–D75CrossRefGoogle Scholar
  145. van Baarlen P, van Belkum A, Summerbell RC, Crous PW, Thomma BPHJ (2007) Molecular mechanisms of pathogenicity: how do pathogenic microorganisms develop cross-kingdom host jumps? FEMS Microbiol Rev 31:239–277PubMedCrossRefPubMedCentralGoogle Scholar
  146. van der Zee A, Mooi F, Van Embden J, Musser J (1997) Molecular evolution and host adaptation of Bordetella spp.: phylogenetic analysis using multilocus enzyme electrophoresis and typing with three insertion sequences. J Bacteriol 179:6609–6617PubMedPubMedCentralCrossRefGoogle Scholar
  147. Vernikos GS, Parkhill J (2006) Interpolated variable order motifs for identification of horizontally acquired DNA: revisiting the Salmonella pathogenicity islands. Bioinformatics 22:2196–2203PubMedCrossRefPubMedCentralGoogle Scholar
  148. Vernikos G, Medini D, Riley DR, Tettelin H (2015) Ten years of pan-genome analyses. Curr Opin Microbiol 23:148–154PubMedCrossRefPubMedCentralGoogle Scholar
  149. Wattam AR, Davis JJ, Assaf R, Boisvert S, Brettin T et al (2017) Improvements to PATRIC, the all-bacterial Bioinformatics Database and Analysis Resource Center. Nucleic Acids Res 45:D535–D542PubMedCrossRefPubMedCentralGoogle Scholar
  150. Weyrich LS, Rolin OY, Muse SJ, Park J, Spidale N et al (2012) A type VI secretion system encoding locus is required for Bordetella bronchiseptica immunomodulation and persistence in vivo. PLoS One 7:e45892PubMedPubMedCentralCrossRefGoogle Scholar
  151. Wiedenbeck J, Cohan FM (2011) Origins of bacterial diversity through horizontal genetic transfer and adaptation to new ecological niches. FEMS Microbiol Rev 35:957–976PubMedCrossRefPubMedCentralGoogle Scholar
  152. Williams MM, Sen KA, Weigand MR, Skoff TH, Cunningham VA et al (2016) Bordetella pertussis strain lacking pertactin and pertussis toxin. Emerg Infect Dis 22:319–322PubMedPubMedCentralCrossRefGoogle Scholar
  153. Wirsing von Koenig CH, Guiso N (2017) Global burden of pertussis: signs of hope but need for accurate data. Lancet Infect Dis 17:889–890CrossRefGoogle Scholar
  154. Wong KK, McClelland M, Stillwell LC, Sisk EC, Thurston SJ et al (1998) Identification and sequence analysis of a 27-kilobase chromosomal fragment containing a Salmonella pathogenicity island located at 92 minutes on the chromosome map of Salmonella enterica serovar typhimurium LT2. Infect Immun 66:3365–3371PubMedPubMedCentralGoogle Scholar
  155. Wood MW, Jones MA, Watson PR, Hedges S, Wallis TS et al (1998) Identification of a pathogenicity island required for Salmonella enteropathogenicity. Mol Microbiol 29:883–891PubMedCrossRefPubMedCentralGoogle Scholar
  156. Wright GD (2010) The antibiotic resistome. Expert Opin Drug Discovery 5:779–788CrossRefGoogle Scholar
  157. Wu HJ, Wang AHJ, Jennings MP (2008) Discovery of virulence factors of pathogenic bacteria. Curr Opin Chem Biol 12:93–101PubMedCrossRefPubMedCentralGoogle Scholar
  158. Yeung KHT, Duclos P, Nelson EAS, Hutubessy RCW (2017) An update of the global burden of pertussis in children younger than 5 years: a modelling study. Lancet Infect Dis 17:974–980PubMedCrossRefPubMedCentralGoogle Scholar
  159. Zankari E, Hasman H, Cosentino S, Vestergaard M, Rasmussen S et al (2012) Identification of acquired antimicrobial resistance genes. J Antimicrob Chemother 67:2640e4CrossRefGoogle Scholar
  160. Zheng LL, Li YX, Ding J, Guo XK, Feng KY et al (2012) A comparison of computational methods for identifying virulence factors. PLoS ONE 7:e42517PubMedPubMedCentralCrossRefGoogle Scholar
  161. Zhou CE, Smith J, Lam M, Zemla A, Dyer MD et al (2007) MvirDB- a microbial database of protein toxins, virulence factors and antibiotic resistance genes for bio-defense applications. Nucleic Acids Res 35:D391–D394PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Jhasketan Badhai
    • 1
  • Sushanta Deb
    • 1
  • Subrata K. Das
    • 1
    Email author
  1. 1.Division of Molecular MicrobiologyInstitute of Life SciencesBhubaneswarIndia

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