Abstract
Genome sequencing, the determination of the complete complement of DNA in an organism, is revolutionizing all aspects of the biological sciences. Genome sequences make available for scientific scrutiny the complete genetic capacity of an organism. With respect to microbes, this means we now have the unprecedented opportunity to investigate the molecular basis of commensal and virulence behavior. We now have genome sequences for a wide range of bacterial pathogens (obligate, facultative, and opportunistic); this has facilitated the discovery of many previously unidentified determinants of pathogenicity and has provided novel insights into what creates a pathogen. In-depth analyses of bacterial genomes are also providing new perspectives on bacterial physiology, molecular adaptation to a preferred niche, and genomic susceptibility to the uptake of foreign DNA, three key factors that can play a significant role in determining whether a species, or a strain, will have pathogenic potential.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Wassenaar, T. M. and Gaastra, W. (2001) Bacterial virulence: can we draw the line? FEMS Microbiol. Lett. 201, 1–7.
Moxon, R. and Tang, C. (2000) Challenge of investigating biologically relevant functions of virulence factors in bacterial pathogens. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 355, 643–656.
Groisman, E. A. and Ochman, H. (1997) How Salmonella became a pathogen. Trends Microbiol. 5, 343–349.
Groisman, E. A. and Ochman, H. (1994) How to become a pathogen. Trends Microbiol. 2, 289–294.
Fleischmann, R. D., Adams, M. D., White, O., Clayton, R. A., Kirkness, E. F., Kerlavage, A. R., et al. (1995) Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science 269, 496–512.
Fraser, C. M., Norris, S. J., Weinstock, G. M., White, O., Sutton, G. G., Dodson, R., et al. (1998) Complete genome sequence of Treponema pallidum, the syphilis spirochete. Science 281, 375–388.
Nowak, R. (1995) Bacterial genome sequence bagged. Science 269, 468–470.
Bentley, S. D., Chater, K. F., Cerdeno-Tarraga, A. M., Challis, G. L., Thomson, N. R., James, K. D., et al. (2002) Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2). Nature 417, 141–147.
Goffeau, A., Barrell, B. G., Bussey, H., Davis, R. W., Dujon, B., Feldmann, H., et al. (1996) Life with 6000 genes. Science 546, 63–67.
Bernal, A., Ear, U., and Kyrpides, N. (2001) Genomes OnLine Database (GOLD): a monitor of genome projects world-wide. Nucleic Acids Res. 29, 126–127.
Cole, S. T., Eiglmeier, K., Parkhill, J., James, K. D., Thomson, N. R., Wheeler, P. R., et al. (2001) Massive gene decay in the leprosy bacillus. Nature 409, 1007–1011.
Read, T. D., Brunham, R. C., Shen, C., Gill, S. R., Heidelberg, J. F., White, O., et al. (2000) Genome sequences of Chlamydia trachomatis MoPn and Chlamydia pneumoniae AR39. Nucleic Acids Res. 28, 1397–1406.
Chambaud, I., Heilig, R., Ferris, S., Barbe, V., Samson, D., Galisson, F., et al. (2001) The complete genome sequence of the murine respiratory pathogen Mycoplasma pulmonis. Nucleic Acids Res. 29, 2145–2153.
McClelland, M., Sanderson, K. E., Spieth, J., Clifton, S. W., Latreille, P., Courtney, L., et al. (2001) Complete genome sequence of Salmonella enterica serovar Typhimurium LT2. Nature 413, 852–856.
Field, D., Hood, D., and Moxon, R. (1999) Contribution of genomics to bacterial pathogenesis. Curr. Opin. Genet. Dev. 9, 700–703.
Kalman, S., Mitchell, W., Marathe, R., Lammel, C., Fan, J., Hyman, R. W., et al. (1999) Comparative genomes of Chlamydia pneumoniae and C. trachomatis. Nat. Genet. 21, 385–389.
Blattner, F. R., Plunkett, G., 3rd, Bloch, C. A., Perna, N. T., Burland, V., Riley, M., et al. (1997) The complete genome sequence of Escherichia coli K-12. Science 277, 1453–1474.
Perna, N. T., Plunkett, G., 3rd, Burland, V., Mau, B., Glasner, J. D., Rose, D. J., et al. (2001) Genome sequence of enterohaemorrhagic Escherichia coli O157:H7. Nature 409, 529–533.
Hayashi, T., Makino, K., Ohnishi, M., Kurokawa, K., Ishii, K., Yokoyama, K., et al. (2001) Complete genome sequence of enterohemorrhagic Escherichia coli O157:H7 and genomic comparison with a laboratory strain K-12. DNA Res. 8, 11–22.
Moxon, R. and Rappuoli, R. (2002) Bacterial pathogen genomics and vaccines. Br. Med. Bull. 62, 45–58.
Pizza, M., Scarlato, V., Masignani, V., Giuliani, M. M., Arico, B., Comanducci, M., et al. (2000) Identification of vaccine candidates against serogroup B meningococcus by whole-genome sequencing. Science 287, 1816–1820.
Tettelin, H., Saunders, N. J., Heidelberg, J., Jeffries, A. C., Nelson, K. E., Eisen, J. A., et al. (2000) Complete genome sequence of Neisseria meningitidis serogroup B strain MC58. Science 287, 1809–1815.
Fraser, C. M., Gocayne, J. D., White, O., Adams, M. D., Clayton, R. A., Fleischmann, R. D., et al. (1995) The minimal gene complement of Mycoplasma genitalium. Science 270, 397–403.
Hutchison, C. A., Peterson, S. N., Gill, S. R., Cline, R. T., White, O., Fraser, C. M., et al. (1999) Global transposon mutagenesis and a minimal Mycoplasma genome. Science 286, 2165–2169.
Fleischmann, R. D., Alland, D., Eisen, J. A., Carpenter, L., White, O., Peterson, J., et al. (2002) Whole-genome comparison of Mycobacterium tuberculosis clinical and laboratory strains. J. Bact. 184, 5479–5490.
Joyce, E. A., Chan, K., Salama, N. R., and Falkow, S. (2002) Redefining bacterial populations: a post-genomic reformation. Nat. Rev. Genet. 3, 462–473.
Heidelberg, J. F., Eisen, J. A., Nelson, W. C., Clayton, R. A., Gwinn, M. L., Dodson, R. J., et al. (2000) DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae. Nature 406, 477–483.
Lan, R. and Reeves, P. R. (2000) Intraspecies variation in bacterial genomes: the need for a species genome concept. Trends Microbiol. 8, 396–401.
Lan, R. and Reeves, P. R. (2001) When does a clone deserve a name? A perspective on bacterial species based on population genetics. Trends Microbiol. 9, 419–424.
Miller, W. (2001) Comparison of genomic DNA sequences: solved and unsolved problems. Bioinformatics 17, 391–397.
Overbeek, R., Fonstein, M., D’Souza, M., Pusch, G. D., and Maltsev, N. (1999) The use of gene clusters to infer functional coupling. Proc. Natl. Acad. Sci. USA 96, 2896–2901.
Stover, C. K., Pham, X. Q., Erwin, A. L., Mizoguchi, S. D., Warrener, P., Hickey, M. J., et al. (2000) Complete genome sequence of Pseudomonas aeruginosa PA01, an opportunistic pathogen. Nature 406, 959–964.
Bayliss, C. D., Field, D., and Moxon, E. R. (2001) The simple sequence contingency loci of Haemophilus influenzae and Neisseria meningitidis. J. Clin. Invest. 107, 657–662.
Schilling, C. H., Covert, M. W., Famili, I., Church, G. M., Edwards, J. S., and Palsson, B. O. (2002) Genome-scale metabolic model of Helicobacter pylori 26695. J. Bacteriol. 184, 4582–4593.
Edwards, J. S. and Palsson, B. O. (2000) The Escherichia coli MG1655 in silico metabolic genotype: its definition, characteristics, and capabilities. Proc. Natl. Acad. Sci. USA 97, 5528–5533.
Oliver, S. G. (1996) From DNA sequence to biological function. Nature 379, 597–600.
Fischer, D. and Eisenberg, D. (1999) Finding families for genomic ORFans. Bioinformatics 15, 759–762.
Doolittle, R. F. (2002) Biodiversity: microbial genomes multiply. Nature 416, 697–700.
Salama, N., Guillemin, K., McDaniel, T. K., Sherlock, G., Tompkins, L., and Falkow, S. (2000) A whole-genome microarray reveals genetic diversity among Helicobacter pylori strains. Proc. Natl. Acad. Sci. USA 97, 14,668–14,673.
Huynen, M. A., Diaz-Lazcoz, Y., and Bork, P. (1997) Differential genome display. Trends Genet. 13, 389–390.
Casjens, S. (1998) The diverse and dynamic structure of bacterial genomes. Annu. Rev. Genet. 32, 339–377.
Tamas, I., Klasson, L. M., Sandstrom, J. P., and Andersson, S. G. (2001) Mutualists and parasites: how to paint yourself into a (metabolic) corner. FEBS Lett. 498, 135–139.
Andersson, J. O. and Andersson, S. G. (1999) Insights into the evolutionary process of genome degradation. Curr. Opin. Genet. Dev. 9, 664–671.
Andersson, S. G., Zomorodipour, A., Andersson, J. O., Sicheritz-Ponten, T., Alsmark, U. C., Podowski, R. M., et al. (1998) The genome sequence of Rickettsia prowazekii and the origin of mitochondria. Nature 396, 133–140.
Ochman, H., Lawrence, J. G., and Groisman, E. A. (2000) Lateral gene transfer and the nature of bacterial innovation. Nature 405, 299–304.
Eisen, J. A. (2000) Horizontal gene transfer among microbial genomes: new insights from complete genome analysis. Curr. Opin. Genet. Dev. 10, 606–611.
Nelson, K. E., Clayton, R. A., Gill, S. R., Gwinn, M. L., Dodson, R. J., Haft, D. H., et al. (1999) Evidence for lateral gene transfer between Archaea and bacteria from genome sequence of Thermotoga maritime. Nature 399, 323–329.
Smoot, J. C., Barbian, K. D., Van Gompel, J. J., Smoot, L. M., Chaussee, M. S., Sylva, G. L., et al. (2002) Genome sequence and comparative microarray analysis of serotype M18 group A Streptococcus strains associated with acute rheumatic fever outbreaks. Proc. Natl. Acad. Sci. USA 99, 4668–4673.
Knapp, S., Hacker, J., Jarchau, T., and Goebel, W. (1986) Large, unstable inserts in the chromosome affect virulence properties of uropathogenic Escherichia coli O6 strain 536. J. Bacteriol. 168, 22–30.
Finlay, B. B. and Falkow, S. (1997) Common themes in microbial pathogenicity revisited. Microbiol. Mol. Biol. Rev. 61, 136–169.
Graham, D. E., Overbeek, R., Olsen, G. J., and Woese, C. R. (2000) An archaeal genomic signature. Proc. Natl. Acad. Sci. USA 97, 3304–3308.
Weinstock, G. M. (2000) Genomics and bacterial pathogenesis. Emerg. Infect. Dis. 6, 496–504.
Chizhikov, V., Rasooly, A., Chumakov, K., and Levy, D. D. (2001) Microarray analysis of microbial virulence factors. Appl. Environ. Microbiol. 67, 3258–3263.
Mitchell, T. J. (1998) Molecular basis of virulence. Arch. Dis. Child. 78, 197–199; discussion 99–200.
Fraser, C. M., Casjens, S., Huang, W. M., Sutton, G. G., Clayton, R., Lathigra, R., et al. (1997) Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi. Nature 390, 580–586.
Cole, S. T., Brosch, R., Parkhill, J., Garnier, T., Churcher, C., Harris, D., et al. (1998) Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393, 537–544.
Wizemann, T. M., Heinrichs, J. H., Adamou, J. E., Erwin, A. L., Kunsch, C., Choi, G. H., et al. (2001) Use of a whole genome approach to identify vaccine molecules affording protection against Streptococcus pneumoniae infection. Infect. Immun. 69, 1593–1598.
De Bolle, X., Bayliss, C. D., Field, D., van de Ven, T., Saunders, N. J., Hood, D. W., et al. (2000) The length of a tetranucleotide repeat tract in Haemophilus influenzae determines the phase variation rate of a gene with homology to type III DNA methyltransferases. Mol. Microbiol. 35, 211–222.
Moxon, E. R., Rainey, P. B., Nowak, M. A., and Lenski, R. E. (1994) Adaptive evolution of highly mutable loci in pathogenic bacteria. Curr. Biol. 4, 24–33.
Hood, D. W., Deadman, M. E., Jennings, M. P., Bisercic, M., Fleischmann, R. D., Venter, J. C., et al. (1996) DNA repeats identify novel virulence genes in Haemophilus influenzae. Proc. Natl. Acad. Sci. USA 93, 11,121–11,125.
Weiser, J. N. (2000) The generation of diversity by Haemophilus influenzae. Trends Microbiol. 8, 433–435.
Tomb, J. F., White, O., Kerlavage, A. R., Clayton, R. A., Sutton, G. G., Fleischmann, R. D., et al. (1997) The complete genome sequence of the gastric pathogen Helicobacter pylori. Nature 388, 539–547.
Parkhill, J., Wren, B. W., Mungall, K., Ketley, J. M., Churcher, C., Basham, D., et al. (2000) The genome sequence of the food-borne pathogen Campylobacter jejuni reveals hypervariable sequences. Nature 403, 665–668.
Parkhill, J., Achtman, M., James, K. D., Bentley, S. D., Churcher, C., Klee, S. R., et al. (2000) Complete DNA sequence of a serogroup A strain of Neisseria meningitidis Z2491. Nature 404, 502–506.
Tettelin, H., Nelson, K. E., Paulsen, I. T., Eisen, J. A., Read, T. D., Peterson, S., et al. (2001) Complete genome sequence of a virulent isolate of Streptococcus pneumoniae. Science 293, 498–506.
Dziejman, M., Balon, E., Boyd, D., Fraser, C. M., Heidelberg, J. F., and Mekalanos, J. J. (2002) Comparative genomic analysis of Vibrio cholerae: genes that correlate with cholera endemic and pandemic disease. Proc. Natl. Acad. Sci. USA 99, 1556–1561.
Dorrell, N., Mangan, J. A., Laing, K. G., Hinds, J., Linton, D., Al-Ghusein, H., et al. (2001) Whole genome comparison of Campylobacter jejuni human isolates using a low-cost microarray reveals extensive genetic diversity. Genome Res. 11, 1706–1715.
Behr, M. A., Wilson, M. A., Gill, W. P., Salamon, H., Schoolnik, G. K., Rane, S., et al. (1999) Comparative genomics of BCG vaccines by whole-genome DNA microarray. Science 284, 1520–1523.
Riley, M. (1993) Functions of the gene products of Escherichia coli. Microbiol. Rev. 57, 862–952.
Fraser, C. M., Eisen, J., Fleischmann, R. D., Ketchum, K. A., and Peterson, S. (2000) Comparative genomics and understanding of microbial biology. Emerg. Infect. Dis. 6, 505–512.
Shimizu, T., Ohtani, K., Hirakawa, H., Ohshima, K., Yamashita, A., Shiba, T., et al. (2002) Complete genome sequence of Clostridium perfringens, an anaerobic flesh-eater. Proc. Natl. Acad. Sci. USA 99, 996–1001.
Kapatral, V., Anderson, I., Ivanova, N., Reznik, G., Los, T., Lykidis, A., et al. (2002) Genome sequence and analysis of the oral bacterium Fusobacterium nucleatum strain ATCC 25586. J. Bact. 184, 2005–2018.
Smith, H. O., Tomb, J. F., Dougherty, B. A., Fleischmann, R. D., and Venter, J. C. (1995) Frequency and distribution of DNA uptake signal sequences in the Haemophilus influenzae Rd genome. Science 269, 538–540.
Frank, A. C., Amiri, H., and Andersson, S. G. (2002) Genome deterioration: loss of repeated sequences and accumulation of junk DNA. Genetica 115, 1–12.
Kuroda, M., Ohta, T., Uchiyama, I., Baba, T., Yuzawa, H., Kobayashi, I., et al. (2001) Whole genome sequencing of meticillin-resistant Staphylococcus aureus. Lancet 357, 1225–1240.
Glaser, P., Frangeul, L., Buchrieser, C., Rusniok, C., Amend, A., Baquero, F., et al. (2001) Comparative genomics of Listeria species. Science 294, 849–852.
Thompson, J. N. (1999) The evolution of species interactions. Science 284, 2116–2118.
Stein, L. (2002) Creating a bioinformatics nation. Nature 417, 119–120.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2004 Humana Press Inc.
About this protocol
Cite this protocol
Field, D., Hughes, J., Moxon, E.R. (2004). Using the Genome to Understand Pathogenicity. In: Woodford, N., Johnson, A.P. (eds) Genomics, Proteomics, and Clinical Bacteriology. Methods in Molecular Biology™, vol 266. Humana Press. https://doi.org/10.1385/1-59259-763-7:261
Download citation
DOI: https://doi.org/10.1385/1-59259-763-7:261
Publisher Name: Humana Press
Print ISBN: 978-1-58829-218-6
Online ISBN: 978-1-59259-763-5
eBook Packages: Springer Protocols