Abstract
Genome analysis of microbial pathogens has provided unique insights into their virulence, host adaptation and evolution. Common themes have emerged, including lateral gene transfer among enteric pathogens, genome decay among obligate intracellular pathogens and antigenic variation among mucosal pathogens. The advent of post-genomic approaches and the sequencing of the human genome will enable scientists to investigate the complex and dynamic interplay between host and pathogen. This wealth of information will catalyse the development of new intervention strategies to reduce the burden of microbial-related disease.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$189.00 per year
only $15.75 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Blaser, M. J. Linking Helicobacter pylori to gastric cancer. Nature Med. 6, 376–377 ( 2000).
Rosenfeld, M. E. et al. Chlamydia, inflammation, and atherogenesis. J. Infect. Dis. 181, S492–S497 (2000).
Fleischmann, R. D. et al. Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science 269, 496– 512 (1995).First sequencing of a free-living organism and first description of use of the shotgun strategy for whole genome sequencing.
Tomb, J. F. et al. The complete genome sequence of the gastric pathogen Helicobacter pylori. Nature 388, 539– 547 (1997).
Alm, R. A. et al. Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori. Nature 397, 176–180 (1999). Sequence determination of a second strain within a species. Identification of a genome plasticity zone.
Tettelin, H. et al. Complete genome sequence of Neisseria meningitidis serogroup B strain MC58. Science 287, 1809 –1815 (2000).
Parkhill, J. et al. Complete DNA sequence of a serogroup A strain of Neisseria meningitidis Z2491. Nature 404, 502– 506 (2000).
Stephens, R. S. et al. Genome sequence of an obligate intracellular pathogen of humans: Chlamydia trachomatis. Science 282, 754–759 (1998).
Read, T. D. et al. Genome sequences of Chlamydia trachomatis MoPn and Chlamydia pneumoniae AR39. Nucleic Acids Res. 28 , 1397–1406 (2000).
Glaser, P. & Cossart, P. The Listeria monocytogenes genome project. Genomes 2000: International conference on microbial and model genomes 20 (2000).
Fraser, C. M. & Fleischmann, R. D. Strategies for whole microbial genome sequencing and analysis. Electrophoresis 18, 1207–1216 (1997).
Frangeul, L. et al. Cloning and assembly strategies in microbial genome projects . Microbiology 145, 2625– 2634 (1999).
Cole, S. T. et al. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393, 537–544 (1998).
Parkhill, J. et al. The genome sequence of the food-borne pathogen Campylobacter jejuni reveals hypervariable sequences. Nature 403, 665–668 (2000). Sequencing Campylobacter jejuni allowed the direct identification of contingency genes from the shotgun sequence.
Hood, D. W. et al. Use of the complete genome sequence information of Haemophilus influenzae strain Rd to investigate lipopolysaccharide biosynthesis. Mol. Microbiol. 22, 951–965 (1996).First example of the exploitation of genome sequence data to investigate the biology of a pathogenic organism.
Linton, D. et al. Phase variation of a β-1,3 galactosyltransferase involved in generation of the ganglioside GM1-like lipo-oligosaccharide of Campylobacter jejuni. Mol. Microbiol. 37, 501– 515 (2000).
Linton, D. et al. Multiple N-acetyl neuraminic acid synthetase (neuB ) genes in Campylobacter jejuni: identification and characterization of the gene involved in sialylation of lipo-oligosaccharide. Mol. Microbiol. 35, 1120–1134 (2000).
Karlyshev, A. V., Linton, D., Gregson, N. A., Lastovica, A. J. & Wren, B. W. Genetic and biochemical evidence of a Campylobacter jejuni capsular polysaccharide that accounts for Penner serotype specificity. Mol. Microbiol. 35, 529–541 (2000).
Wren, B. W. et al. Characterization of a haemolysin from Mycobacterium tuberculosis with homology to a virulence factor of Serpulina hyodysenteriae. Microbiology 144, 1205–1211 (1998).
Heidelberg, J. F. et al. DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae, Nature 406, 477– 483 (2000).
Fraser, C. M. et al. Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi. Nature 390, 580– 586 (1997).
Blattner, F. R. et al. The complete genome sequence of Escherichia coli K-12 . Science 277, 1453–1474 (1997).
Ochman, H., Lawrence, J. G. & Groisman, E. A. Lateral gene transfer and the nature of bacterial innovation. Nature 405, 299– 304 (2000).
Hacker, J., Blum-Oehler, G., Muhldorfer, I. & Tschape, H. Pathogenicity islands of virulent bacteria: structure, function and impact on microbial evolution. Mol. Microbiol. 23, 1089–1097 (1997).
Cheng, L. W. & Schneewind, O. Type III machines of Gram-negative bacteria: delivering the goods. Trends Microbiol. 8 , 214–220 (2000).
Galan, J. E. & Collmer, A. Type III secretion machines: bacterial devices for protein delivery into host cells. Science 284, 1322–1328 (1999).
Covacci, A., Telford, J. L., Del Giudice, G., Parsonnet, J. & Rappuoli, R. Helicobacter pylori virulence and genetic geography. Science 284, 1328 –1333 (1999).
Saunders, N. J., Peden, J. F., Hood, D. W. & Moxon, E. R. Simple sequence repeats in the Helicobacter pylori genome. Mol. Microbiol. 27, 1091–1098 (1998).
Ferretti, J. J. et al. The complete genome sequence of an M1 strain of Streptococcus pyogenes. Genomes 2000: International conference on microbial and model genomes 21 (2000).
Andersson, S. G. et al. The genome sequence of Rickettsia prowazekii and the origin of mitochondria. Nature 396, 133– 140 (1998).Analysis of the genome sequence of the obligate intracellular pathogen Rickettsia prowazekii revealed extensive genome downsizing and the possible origins of mitochondria.
Andersson, J. O. & Andersson, S. G. E. A century of typhus, lice and Rickettsia. Res. Microbiol. 151, 143–150 (2000).
Brosch, R., Gordon, S. V., Eiglmeier, K., Garnier, T. & Cole, S. T. Comparative genomics of the leprosy and tubercle bacilli. Res. Microbiol. 151, 135–142 (2000).
Fraser, C. M. et al. Complete genome sequence of Treponema pallidum, the syphilis spirochete. Science 281, 375– 388 (1998).
Buchrieser, C. et al. The 102-kilobase pgm locus of Yersinia pestis: sequence analysis and comparison of selected regions among different Yersinia pestis and Yersinia pseudotuberculosis strains. Infect. Immunol. 67, 4851–4861 ( 1999).
Achtman, M. et al. Yersinia pestis, the cause of plague, is a recently emerged clone of Yersinia pseudotuberculosis. Proc. Natl Acad. Sci. USA 96, 14043–14048 (1999).
Fraser, C. M. et al. The minimal gene complement of Mycoplasma genitalium. Science 270, 397–403 ( 1995).
Hutchison, C. A. et al. Global transposon mutagenesis and a minimal Mycoplasma genome. Science 286, 2165– 2169 (1999).
Henderson, I. R., Owen, P. & Nataro, J. P. Molecular switches—the ON and OFF of bacterial phase variation. Mol. Microbiol. 33, 919 –932 (1999).
Moxon, E. R., Rainey, P. B., Nowak, M. A. & Lenski, R. E. Adaptive evolution of highly mutable loci in pathogenic bacteria. Curr. Biol. 4, 24–33 ( 1994).
Hood, D. W. et al. DNA repeats identify novel virulence genes in Haemophilus influenzae. Proc. Natl Acad. Sci. USA 93, 11121–11125 (1996). Demonstration of the rapid identification of repeat sequences for the convenient identification of new virulence determinants.
Wang, G., Rasko, D. A., Sherburne, R. & Taylor, D. E. Molecular genetic basis for the variable expression of Lewis Y antigen. in Helicobacter pylori: analysis of the alpha (1,2) fucosyltransferase gene . Mol. Microbiol. 31, 1265– 1274 (1999).
Appelmelk, B. J. et al. Phase variation in Helicobacter pylori lipopolysaccharide due to changes in the lengths of poly(C) tracts in alpha3-fucosyltransferase genes. Infect. Immunol. 67, 5361– 5366 (1999).
Wang, G., Ge, Z., Rasko, D. A. & Taylor, D. E. Lewis antigens in Helicobacter pylori: biosynthesis and phase variation. Mol. Microbiol. 36, 1187–1196 (2000).
Saunders, N. J. et al. Repeat-associated phase variable genes in the complete genome sequence of Neisseria meningitis strain MC58. Mol. Microbiol. 37, 207–215 ( 2000).
De Bolle, X. et al. 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 (2000).
Park, S. F., Purdy, D. & Leach, S. Localized reversible frameshift mutation in the flhA gene confers phase variability to flagellin gene expression in Campylobacter coli. J. Bacteriol. 182, 207– 210 (2000).
Barry, M. A., Lai, W. C. & Johnston, S. A. Protection against mycoplasma infection using expression-library immunization. Nature 377, 632– 635 (1995).
Pizza, M. et al. Identification of vaccine candidates against serogroup B meningococcus by whole-genome sequencing. Science 287, 1816–1820 (2000). Remarkable demonstration of the use of whole-genome sequence data from an important pathogen Neisseria meningitidis to identify seven conserved surface antigens as vaccine candidates.
Hensel, M. et al. Simultaneous identification of bacterial virulence genes by negative selection. Science 269, 400– 403 (1995).First description of signature-tagged mutagenesis which allowed the identification of a second type III secretion system (spiII) in Salmonella typhimurium.
Shea, J. E., Hensel, M., Gleeson, C. & Holden, D. W. Identification of a virulence locus encoding a second type III secretion system in Salmonella typhimurium. Proc. Natl Acad. Sci. USA 93, 2593–2597 (1996).
Mei, J. M., Nourbakhsh, F., Ford, C. W. & Holden, D. W. Identification of Staphylococcus aureus virulence genes in a murine model of bacteraemia using signature-tagged mutagenesis. Mol. Microbiol. 26, 399–407 ( 1997).
Chiang, S. L. & Mekalanos, J. J. Use of signature-tagged transposon mutagenesis to identify Vibrio cholerae genes critical for colonization . Mol. Microbiol. 27, 797– 805 (1998).
Claus, H., Frosch, M. & Vogel, U. Identification of a hotspot for transformation of Neisseria meningitidis by shuttle mutagenesis using signature-tagged transposons . Mol. Gen. Genet. 259, 363– 371 (1998).
Polissi, A. et al. Large-scale identification of virulence genes from Streptococcus pneumoniae. Infect. Immunol. 66, 5620 –5629 (1998).
Edelstein, P. H., Edelstein, M. A., Higa, F. & Falkow, S. Discovery of virulence genes of Legionella pneumophila by using signature tagged mutagenesis in a guinea pig pneumonia model. Proc. Natl Acad. Sci. USA 96, 8190–8195 (1999).
Darwin, A. J. & Miller, V. L. Identification of Yersinia enterocolitica genes affecting survival in an animal host using signature-tagged transposon mutagenesis. Mol. Microbiol. 32, 51–62 (1999).
Camacho, L. R., Ensergueix, D., Perez, E., Gicquel, B. & Guilhot, C. Identification of a virulence gene cluster of Mycobacterium tuberculosis by signature-tagged transposon mutagenesis. Mol. Microbiol. 34, 257– 267 (1999).
Zhao, H., Li, X., Johnson, D. E. & Mobley, H. L. Identification of protease and rpoN-associated genes of uropathogenic Proteus mirabilis by negative selection in a mouse model of ascending urinary tract infection . Microbiology 145, 185– 195 (1999).
Ogasawara, N. Systematic functional mutagenesis of Bacillus subtilis genes. Res. Microbiol. 152, 129–134 (2000).
Winzeler, E. A. et al. Functional characterization of the Saccharomyces cerevisiae genome by gene deletion and parallel analysis. Science 285, 901–906 (1999).
Brown, P. O. & Botstein, D. Exploring the new world of the genome with DNA microarrays. Nature Genet. 21, 33–37 (1999).
Mahan, M.J., Slauch, J. M. & Mekalanous, J. J. Selection of bacterial virulence genes that are specifically induced in host tissues. Science 259, 686 –688 (1993).
Valdivia, R. H. & Falkow, S. Fluorescence-based isolation of bacterial genes expressed within host cells. Science 277, 2007–2011 ( 1993).
Strauss, E. J., Falkow, S. Microbial pathogenesis: genomics and beyond. Science 276, 707– 712 (1997).
Pappin, D. J. Peptide mass fingerprinting using MALDI-TOF mass spectrometry. Methods Mol. Biol. 64, 165–173 (1997).
Fernandez, J., Gharahdaghi, F. & Mische, S. M. Routine identification of proteins from sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) gels or polyvinyl difluoride membranes using matrix assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS). Electrophoresis 19, 1036–1045 (1998).
Qi, S. Y., Moir, A. & O'Connor, C. D. Proteome of Salmonella typhimurium SL1344: identification of novel abundant cell envelope proteins and assignment to a two-dimensional reference map. J. Bacteriol. 178, 5032–5038 (1996).
Wasinger, V. C., Pollack, J. D. & Humphery-Smith, I. The proteome of Mycoplasma genitalium Chaps-soluble component. Eur. J. Biochem. 267, 1571– 1582 (2000).
O'Connor, C. D., Farris, M., Fowler, R. & Qi, S. Y. The proteome of Salmonella enterica serovar typhimurium: current progress on its determination and some applications. Electrophoresis 18, 1483–1490 (1997).
Sonnenberg, M. G. & Belisle, J. T. Definition of Mycobacterium tuberculosis culture filtrate proteins by two-dimensional polyacrylamide gel electrophoresis, N-terminal amino acid sequencing, and electrospray mass spectrometry. Infect. Immunol. 65 , 4515–4524 (1997).
Jungblut, P. R. et al. Comparative proteome analysis of Mycobacterium tuberculosis and Mycobacterium bovis BCG strains: towards functional genomics of microbial pathogens. Mol. Microbiol. 33, 1103–1117 (1999).
Tekaia, F. et al. Analysis of the proteome of Mycobacterium tuberculosis in silico. Tuber. Lung Dis. 79, 329– 342 (1999).
Jungblut, P. R. et al. Comparative proteome analysis of Helicobacter pylori. Mol. Microbiol. 36, 710–725 (2000).
Williams, J. M., Chen, G. C., Zhu, L. & Rest, R. F. Using the yeast two-hybrid system to identify human epithelial cell proteins that bind gonococcal Opa proteins: intracellular gonococci bind pyruvate kinase via their Opa proteins and require host pyruvate for growth. Mol. Microbiol. 27, 171–186 (1998).
Hartland, E. L. et al. Binding of intimin from enteropathogenic Escherichia coli to Tir and to host cells. Mol. Microbiol. 32, 151–158 (1999).
Day, J. B. & Plano, G. V. A complex composed of SycN and YscB functions as a specific chaperone for YopN in Yersinia pestis. Mol. Microbiol. 30, 777–788 (1998).
Rain, J. C. & Legrain, P. Functional proteomics on microbial pathogens. Genomes 2000: International conference on microbial and model genomes 26 (2000).
Behr, M. A. et al. Comparative genomics of BCG vaccines by whole-genome DNA microarray . Science 284, 1520–1523 (1999).
Kalman, S. et al. Comparative genomes of Chlamydia pneumoniae and C. trachomatis. Nature Genet. 21, 385 –389 (1999).
Himmelreich, R. et al. Complete sequence analysis of the genome of the bacterium Mycoplasma pneumoniae. Nucleic Acids Res. 24, 4420–4449 (1996).
Stover, C. K. et al. Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen. Nature 406, 959–964 (2000).
Wong, S. M. & Mekalanos, J. J. Genetic footprinting with mariner-based transposition in Pseudomonas aeruginosa. Proc. Natl Acad. Sci. USA 97, 10191–10196 (2000).
Acknowledgements
Work in the author's laboratory is supported by the BBSRC, the Wellcome Trust and Beowulf Genomics. I acknowledge Dennis Linton and Elaine Allan for helpful comments and a critical review of the manuscript.
Author information
Authors and Affiliations
Related links
Related links
GENOME PROJECTS
Campylobacter jejuni NCTC11168
Chlamydia trachomatis D/UW-3/Cx
Mycobacterium tuberculosis H37Rv
Neisseria meningitidis A Z2491
Rickettsia prowazekii Madrid E
FURTHER INFORMATION
Los Alamos sexually transmitted pathogens database
Kyoto encyclopaedia of genes and genomes
Australian proteome analysis facility
The Brown lab microarray guide
Bacterial microarrays at St. George's
ENCYCLOPEDIA OF LIFE SCIENCES
Glossary
- PATHOGEN
-
An organism, generally a microorganism, that can cause disease in animals and plants.
- VIRULENCE FACTOR
-
In the strict sense, a determinant that causes damage to the host cell (for example, an exotoxin). In the broader sense, a determinant required for the survival of the pathogen in the host (for example, the ability to acquire iron).
- IMMUNOGEN
-
An antigen that produces a significant immunological response.
- LATERAL GENE TRANSFER
-
The transfer of DNA, frequently cassettes of genes, between organisms.
- ENTERIC PATHOGEN
-
A pathogen that resides in the gastrointestinal tract.
- COMPETENCE
-
The ability of bacteria to take up exogenous DNA molecules.
- EXOTOXINS
-
Generally secreted proteins that cause damage to the host cell.
- OBLIGATE INTRACELLULAR PATHOGEN
-
A pathogen that lives exclusively within the host, and depends on the host for survival.
- FASTIDIOUS INTRACELLULAR PATHOGEN
-
A pathogen that lives within the host and has stringent growth requirements.
- LEWIS ANTIGENS
-
Fucosylated carbohydrate antigens usually found on the surface of eukaryotic cells. They are structurally related to human ABH blood group systems.
- MUCOSAL PATHOGEN
-
A pathogen that frequents the mucosal surface (for example, nose, lungs and gastrointestinal tract) of the host.
Rights and permissions
About this article
Cite this article
Wren, B. Microbial genome analysis: insights into virulence, host adaptation and evolution. Nat Rev Genet 1, 30–39 (2000). https://doi.org/10.1038/35049551
Issue Date:
DOI: https://doi.org/10.1038/35049551
This article is cited by
-
Serotype-specific evolutionary patterns of antimicrobial-resistant Salmonella enterica
BMC Evolutionary Biology (2019)
-
Comparative evaluation of 16S rRNA gene in world-wide strains of Streptococcus iniae and Streptococcus parauberis for early diagnostic marker
Genes & Genomics (2017)
-
Complete genome sequence and comparative genome analysis of Streptococcus parauberis KCTC11980
Genes & Genomics (2015)
-
Comparative genomics of closely related Salmonella enterica serovar Typhi strains reveals genome dynamics and the acquisition of novel pathogenic elements
BMC Genomics (2014)
-
Modulation of IL-8 Boosted by Mycoplasma pneumoniae lysate in Human Airway Epithelial Cells
Journal of Clinical Immunology (2013)