Abstract
The approach of whole-genome shotgun sequencing coupled with the availability of computational algorithms to facilitate the assembly, gene prediction, and functional annotation of entire genomes has sparked a revolution in our understanding of the biology of free-living organisms. More than 40 bacterial genomes have been sequenced to date, of which several are important human pathogens. The capacity to sequence and assemble entire genomes of bacteria, pathogenic protozoans, and fungi in a rapid and cost-effective way has energized every aspect of microbial science. Comparative genome analysis allows us to dissect the evolutionary forces at work and provides insights into adaptations of microbes to their unique ecological niches. Factors that shape host-pathogen interactions and their outcomes include genetic polymorphisms in the microbial pathogen and host, both of which can impact on microbial virulence or host immune responses to infection. The availability of the genome sequence of entire organisms, together with the use of high-throughput sequence-based genomic technologies to define microbial and host physiological states, provides the unparalleled opportunity to better define clinical outcomes in the field of infectious diseases. There is one overarching lesson: completion of the genomic sequence of any species answers many questions, while at the same time it invites totally new questions.
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References
Adams MD, Dubnick M, Kerlavage AR, et al.: Sequence identification of 2,375 human brain genes. Nature 1992;355:632–634
Fleischmann RD, Adams MD, White O, et al.: Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science 1995;269:496–512
Fraser CM, Eisen JA, Salzberg SL: Microbial genome sequencing. Nature 2000;406:799–803
Venter JC, Adams MD, Myers EW, et al.: The sequence of the human genome. Science 2001;291:1304–1351
Lander ES, Linton LM, Birren B, et al.: Initial sequencing and analysis of the human genome. Nature 2001;409:860–921
Broder S, Venter JC: Sequencing the entire genomes of free-living organisms: The foundation of pharmacology in the new millennium. Annu Rev Pharmacol Toxicol 2000;40:97–132
Cohen ML: Changing patterns of infectious disease. Nature 2000;406:762–767
Ferber D: Antibiotic resistance. Superbugs on the hoof? Science 2000;288:792–794
Blaser MJ, Berg DE: Helicobacter pylori genetic diversity and risk of human disease. J Clin Invest 2001;107:767–773
Costerton JW, Stewart PS, Greenberg EP: Bacterial biofilms: A common cause of persistent infections. Science 1999;284:1318–1322
Altschul SF, Madden TL, Schaffer AA, et al.: Gapped BLAST and PSI-BLAST: A new generation of protein database search programs. Nucleic Acids Res 1997;25:3389–3402
Ponting CP, Schultz J, Milpetz F, Bork P: SMART: Identification and annotation of domains from signalling and extracellular protein sequences. Nucleic Acids Res 1999;27:229–232
Bateman A, Birney E, Durbin R, Eddy SR, Howe KL, Sonnhammer EL: The Pfam protein families database. Nucleic Acids Res 2000;28:263–266
Tatusov RL, Koonin EV, Lipman DJ: A genomic perspective on protein families. Science 1997;278:631–637
Tatusov RL, Natale DA, Garkavtsev IV, et al.: The COG database: New developments in phylogenetic classification of proteins from complete genomes. Nucleic Acids Res 2001;29:22–28
Rubin GM, Yandell MD, Wortman JR, et al.: Comparative genomics of the eukaryotes. Science 2000;287:2204–2215
Cole ST, Brosch R, Parkhill J, et al.: Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 1998;393:537–544
McKinney JD, Honer zu Bentrup K, Munoz-Elias EJ, et al.: Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase. Nature 2000;406:735–738
Cole ST, Eiglmeier K, Parkhill J, et al.: Massive gene decay in the leprosy bacillus. Nature 2001;409:1007–1011
Perna NT, Plunkett G III, Burland V, et al.: Genome sequence of enterohaemorrhagic Escherichia coli O157: H 7. Nature 2001;409:529–533
Blattner FR, Plunkett G III, Bloch CA, et al.: The complete genome sequence of Escherichia coli K-12. Science 1997;277:1453–1474
Kalman S, Mitchell W, Marathe R, et al: Comparative genomes of Chlamydia pneumoniae and C trachomatis. Nat Genet 1999;21:385–389
Fraser CM, Casjens S, Huang WM, et al.: Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi. Nature 1997;390:580–586
Fraser CM, Norris SJ, Weinstock GM, et al.: Complete genome sequence of Treponema pallidum, the syphilis spirochete. Science 1998;281:375–388
Subramanian G, Koonin EV, Aravind L: Comparative genome analysis of the pathogenic spirochetes Borrelia burgdorferi and Treponema pallidum. Infect Immun 2000;68:1633–1648
Ho CK, Shuman S: A yeast-like mRNA capping apparatus in Plasmodium falciparum. Proc Natl Acad Sci U S A 2001;98:3050–3055
Aravind L. Guilt by association: Contextual information in genome analysis. Genome Res 2000;10:1074–1077
Bernard GR, Vincent JL, Laterre PF, et al.: Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001;344:699–709
Hacker J, Kaper JB: Pathogenicity islands and the evolution of microbes. Annu Rev Microbiol 2000;54:641–679
Wren BW: Microbial genome analysis: Insights into virulence, host adaptation and evolution. Nat Rev Genet 2000;1:30–39
Ochman H, Lawrence JG, Groisman EA: Lateral gene transfer and the nature of bacterial innovation. Nature 2000;405:299–304
Gardner MJ, Tettelin H, Carucci DJ, et al.: Chromosome 2 sequence of the human malaria parasite Plasmodium falciparum. Science 1998;282:1126–1132
Hoffman SL, Rogers WO, Carucci DJ, Venter JC: From genomics to vaccines: Malaria as a model system. Nat Med 1998;4:1351–1353
Bachmaier K, Neu N, de la Maza LM, Pal S, Hessel A, Penninger JM: Chlamydia infections and heart disease linked through antigenic mimicry. Science 1999;283:1335–1339
Russo JJ, Bohenzky RA, Chien MC, et al.: Nucleotide sequence of the Kaposi sarcoma-associated herpesvirus (HHV8). Proc Natl Acad Sci U S A 1996;93:14862–14867
Senkevich TG, Koonin EV, Bugert JJ, Darai G, Moss B: The genome of Molluscum contagiosum virus: Analysis and comparison with other poxviruses. Virology 1997;233:19–42
Lorenz E, Mira JP, Cornish KL, Arbour NC, Schwartz DA: A novel polymorphism in the Toll-like receptor 2 gene and its potential association with staphylococcal infection. Infect Immun 2000;68:6398–6401
Li P, Chan HC, He B, et al.: An antimicrobial peptide gene found in the male reproductive system of rats. Science 2001;291:1783–1785
Weatherall D, Clegg J, Kwiatkowski D: The role of genomics in studying genetic susceptibility to infectious disease. Genome Res 1997;7:967–973
Knight JC, Udalova I, Hill AV, et al.: A polymorphism that affects OCT-1 binding to the TNF promoter region is associated with severe malaria. Nat Genet 1999;22:145–150
Bellamy R, Ruwende C, Corrah T, McAdam KP, Whittle HC, Hill AV: Variations in the NRAMP1 gene and susceptibility to tuberculosis in West Africans. N Engl J Med 1998;338:640–644
Dorman SE, Holland SM: Interferon-gamma and interleukin-12 pathway defects and human disease. Cytokine Growth Factor Rev 2000;11:321–333
Littman DR: Chemokine receptors: Keys to AIDS pathogenesis? Cell 1998;93:677–680
Ying L, Katz Y, Schlesinger M, et al.: Complement factor H gene mutation associated with autosomal recessive atypical hemolytic uremic syndrome. Am J Hum Genet 1999;65:1538–1546
Xu H, Iijima K, Shirakawa T, et al.: Platelet-activating factor acetylhydrolase gene mutation in Japanese children with Escherichia coli O157-associated hemolytic uremic syndrome. Am J Kidney Dis 2000;36:42–46
Shi MM: Enabling large-scale pharmacogenetic studies by high-throughput mutation detection and genotyping technologies. Clin Chem 2001;47:164–172
Rudert F: Genomics and proteomics tools for the clinic. Curr Opin Mol Ther 2000;2:633–642
Pandey A, Mann M: Proteomics to study genes and genomes. Nature 2000;405:837–846
Nouwens AS, Cordwell SJ, Larsen MR, et al.: Complementing genomics with proteomics: The membrane subproteome of Pseudomonas aeruginosa PAO 1. Electrophoresis 2000;21:3797–3809
Salama N, Guillemin K, McDaniel TK, Sherlock G, Tompkins L, Falkow S: A whole-genome microarray reveals genetic diversity among Helicobacter pylori strains. Proc Natl Acad Sci U S A 2000;97:14668–14673
Rain JC, Selig L, De Reuse H, et al.: The protein-protein interaction map of Helicobacter pylori. Nature 2001;409:211–215
Wong CS, Jelacic S, Habeeb RL, Watkins SL, Tarr PI: The risk of the hemolytic-uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 infections. N Engl J Med 2000;342:1930–1936
Peterson L, Hamilton J, Baron E, et al.: Role of clinical microbiology laboratories in the management and control of infectious diseases and the delivery of health care. Clin Infect Dis 2001;32:605–611
Alm RA, Ling LS, Moir DT, et al.: Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori. Nature 1999;397:176–180
Parkhill J, Wren BW, Mungall K, et al.: The genome sequence of the food-borne pathogen Campylobacter jejuni reveals hypervariable sequences. Nature 2000;403:665–668
Stover CK, Pham XQ, Erwin AL, et al.: Complete genome sequence of Pseudomonas aeruginosa PA01, an opportunistic pathogen. Nature 2000;406:959–964
Heidelberg JF, Eisen JA, Nelson WC, et al.: DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae. Nature 2000;406:477–483
Tettelin H, Saunders NJ, Heidelberg J, et al.: Complete genome sequence of Neisseria meningitidis serogroup B strain MC 58. Science 2000;287:1809–1815
Stephens RS, Kalman S, Lammel C, et al.: Genome sequence of an obligate intracellular pathogen of humans: Chlamydia trachomatis. Science 1998;282:754–759
Himmelreich R, Hilbert H, Plagens H, Pirkl E, Li BC, Herrmann R: Complete sequence analysis of the genome of the bacterium Mycoplasma pneumoniae. Nucleic Acids Res 1996;24:4420–4449
Fraser CM, Gocayne JD, White O, et al.: The minimal gene complement of Mycoplasma genitalium. Science 1995;270:397–403
Andersson SG, Zomorodipour A, Andersson JO, et al.: The genome sequence of Rickettsia prowazekii and the origin of mitochondria. Nature 1998;396:133–140
Gardner MJ, Tettelin H, Carucci DJ, et al.: The malaria genome sequencing project: Complete sequence of Plasmodium falciparum chromosome 2. Parassitologia 1999;41:69–75
Adams MD, Celniker SE, Holt RA, et al.: The genome sequence of Drosophila melanogaster. Science 2000;287:2185–2195
Ponting CP, Aravind L, Schultz J, Bork P, Koonin EV: Eukaryotic signalling domain homologues in archaea and bacteria. Ancient ancestry and horizontal gene transfer. J Mol Biol 1999;289:729–745
Ponting CP: Chlamydial homologues of the MACPF (MAC/perforin domain. Curr Biol 1999;9: R911–R913
del Portillo HA, Fernandez-Becerra C, Bowman S, et al.: A superfamily of variant genes encoded in the subtelomeric region of Plasmodium vivax. Nature 2001;410:839–842
Lien E, Means TK, Heine H, et al.: Toll-like receptor 4 imparts ligand-specific recognition of bacterial lipopolysaccharide. J Clin Invest 2000;105:497–504
Kisich KO, Heifets L, Higgins M, Diamond G: Antimycobacterial agent based on mRNA encoding human beta-defensin 2 enables primary macrophages to restrict growth of Mycobacterium tuberculosis. Infect Immun 2001;69:2692–2699
Walport MJ: Complement. First of two parts. N Engl J Med 2001;344:1058–1066
Segal BH, Leto TL, Gallin JI, Malech HL, Holland SM: Genetic, biochemical, and clinical features of chronic granulomatous disease. Medicine (Baltimore) 2000;79:170–200
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Subramanian, G., Mural, R., Hoffman, S.L. et al. Microbial Disease in Humans: A Genomic Perspective. Molecular Diagnosis 6, 243–252 (2001). https://doi.org/10.1007/BF03262061
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DOI: https://doi.org/10.1007/BF03262061