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Lateral Gene Transfer (LGT) between Archaea and Escherichia coliis a contributor to the emergence of novel infectious disease
© Faguy; licensee BioMed Central Ltd. 2003
Received: 09 January 2003
Accepted: 19 June 2003
Published: 19 June 2003
Lateral gene transfer is the major mechanism for acquisition of new virulence genes in pathogens. Recent whole genome analyses have suggested massive gene transfer between widely divergent organisms.
Presentation of the hypothesis
Archeal-like genes acting as virulence genes are present in several pathogens and genomes contain a number of archaeal-like genes of unknown function. Archaea, by virtue of their very different evolutionary history and different environment, provide a pool of potential virulence genes to bacterial pathogens.
Testing the hypothesis
We can test this hypothesis by 1)identifying genes likely to have been transferred (directly or indirectly) to E. coli O157:H7 from archaea; 2)investigating the distribution of similar genes in pathogens and non-pathogens and 3)performing rigorous phylogenetic analyses on putative transfers.
Implications of the hypothesis
Although this hypothesis focuses on archaea and E. coli, it will serve as a model having broad applicability to a number of pathogenic systems. Since no archaea are known vertebrate pathogens, archaeal-like transferred genes that are associated with virulence in bacteria represent a clear model for the emergence of virulence genes.
The fact and process of lateral gene transfer (LGT) has been integral to the study of infectious disease since Griffith . Most investigations have, however, centered on transfer of known virulence genes and genes involved in establishing infections (antibiotic resistance, toxins, capsule, etc.) between close relatives who are both pathogens. The explosion of gene sequence information and complete genomes in the last 5 years has reinforced and extended our view of virulence evolution. To quote a review : "lateral transfers have effectively changed the ecological and pathogenic character of bacterial species." Analysis of gene sequence and complete genome information[3–11] have led to the realization that LGT is not a rare exception to classical Darwinian evolution, but may be the predominant mode of evolutionary change in prokaryotes[2, 12–15].
Given the common perception of archaea as extremophiles, one might expect the opportunity for transfer between archaeal organisms and bacterial pathogens to be a rare event. However, many archaea are present in more "normal" environments. Methanogenic archaea are very common in vertebrate and invertebrate digestive systems. In fact, in diary cattle, methanogenic archaea make up a substantial fraction of the micro biota  and E coli O157 is also very common, being cultured from 75% of herds . Furthermore, there are similarities among bacterial and archaeal phages, plasmids, and other vectors for mediating transfer (IS elements; transposable elements). Transfer of DNA in natural environments has been extensively described for a number of different organisms: Bushman (Table 5.5,) lists more than 30 studies. Many different functions – proteases, metabolic genes, oxygen protection genes, secretion systems, transporter genes, iron acquisition systems – can, under the right circumstances, contribute to virulence in an emerging pathogen.
E. coli O157:H7 causes hemorrhagic colitis and hemolytic uremic syndrome. It is widely recognized as a worldwide public health danger. However, it has only been associated with human disease since 1982. There is a complete genome sequence available for E. coli K-12, as well as much genetic information on many other well-studied non-pathogenic E. coli. There are two published complete genomes for E. coli O157:H7 enteropathogenic strains [8, 21], as well as seven E. coli genomes in progress  (GOLD database ). Virulence also depends on many different genes in enterohemorrhagic E. coli . For the purposes of testing the contribution of archaea to virulence genes,E. coli O157:H7 serves as an ideal model.
Testing the hypothesis
We can test this hypothesis by:
1) Identifying genes likely to have been transferred (directly or indirectly) to E. coli O157:H7 from archaea.
2) Investigating the distribution of similar genes in pathogens and non-pathogens and performing rigorous phylogenetic analyses on putative transfers.
Have any transfers been described between archaea and E. coliO157?
I have demonstrated that a gene coding for a bifunctional catalase-peroxidase is likely a transfer from archaea to a variety of pathogenic bacteria, including E. coli O157:H7. Although not yet directly implicated in O157:H7 as a virulence factor, this enzyme has been implicated as a virulence factor in Mycobacterium tuberculosis [24, 26], and in Legionella pneumophila . Furthermore, this E. coli O157:H7 catalase-peroxidase has been associated with enterohaemorrhagic hemolysin in a variety of shiga-like toxin-producing (verotoxin-producing) E. coli [30, 31]. This correlation of the presence of the catalase-peroxidase in many virulent but not in avirulent strains suggests a direct role in the virulence of enterohemorrhagic E. coli.
How can we identify other genes likely to have been transferred (directly or indirectly) to E. coliO157:H7 from archaea?
We can use the three complete E. coli genomes available[8, 20, 21] to identify a subset of genes present in one (or both) of the O157 strains but not in K-12. This subset of genes – although most have not been directly identified as virulence genes – are more likely to be virulence-associated. This subset will be the focus of our search for genes likely to have laterally transferred from archaea. Perna et al  identified 1,387 genes in the EDL933 O157 strain they sequenced that are O157-specific; This number does not include the O157-specific plasmids that were previously sequenced from which some of the preliminary work described below was derived.
As a preliminary step to testing this hypothesis I have searched the E. coli O157:H7 strain EDL933 genome for open reading frames (ORFs) meeting the following criteria:
1) present in O157 strain EDL933 but not in E. coli K-12
2) highly similar (having a BLASTP similarity bit score > 95) to ORFs found in at least two archaeal genomes
3) having few or no highly similar proteins (BLASTP score < 85) in other bacterial genomes
This search was facilitated by the Clusters of Orthologous Groups (COG) database at NCBI [33, 34]. This preliminary, non-systematic search produced 6 ORFS worth considering as LGTs from archaea to pathogenic bacteria. Table 1 shows these ORFs with their location and, if any information was available, a possible function.
Potential Archaeal to Bacterial Laterally Transferred ORFs in E. coli O157:H7 EDL933 Genome. Although ORFs Z5331 and Z0509 do not have archaeal genes as the most similar BLAST hit, they are included because in general they are absent from almost all bacterial genomes.
E. coli O157:H7 designation
Location (O island)
Best BLAST hit to ORF from:
Best guess at function
ABC transporter : cations?
ABC transporter : cations?
Halobacterium sp. NRC-1
Halobacterium sp. NRC-1
Further testing of this hypothesis will require rigorous phylogenetic analyses of each suspected transfer. The procedure of comparing similarity scores to identify potential lateral transfers (used above) although commonly employed[6, 7, 37] it is fraught with potential errors [15, 38–42, 34, 35] and must serve only as an initial screen. Ragan recently wrote:
This study demonstrates the need for a systematic, comprehensive approach to the study of LGT based on first principles, i.e. rigorous inference and statistically based comparison of molecular phylogenetic trees. As more genomic sequences appear, a tree-based approach will become both more challenging and more rewarding.
Implications of the hypothesis
Although this hypothesis focuses on archaea and E. coli, the model of distant gene transfer as a major contributor of "new" virulence genes to pathogens or potential pathogens has broad applicability to a large number of pathogenic systems. Archaea represent both the most distant source and, in many ways, the most unlikely source for virulence genes. If E. coli can acquire virulence genes from archaea, then potentially any organism is a reservoir of virulence genes for pathogens. 
The implications, should this hypothesis be proven, are myriad. Our understanding of potential sources of virulence genes will be expanded to include virtually all life on earth – at first glance a frightening prospect. At the same time, however, it would allow us to move from a descriptive, reactionary view of infectious disease towards a predictive science of infectious disease. It would be dramatic evidence of what some microbiologists suspect: that lateral gene transfer is the predominant engine of variation in prokaryotes and the catalyst for the emergence of new bacterial pathogens.
The author would like to thank E. S. Loker and W. F. Doolittle for helpful discussions and comments on an early version of the manuscript and Hannu Myllykallio and Jacques Ravel for helpful and insightful comments during review. This work was supported by funding from the Research Allocations Committee of the University of New Mexico.
- Griffith F: The significance of pneumococcal types. Journal of Hygiene. 1928, 27: 113-159.View ArticlePubMedPubMed CentralGoogle Scholar
- Ochman H, Lawrence JG, Groisman EA: Lateral gene transfer and the nature of bacterial innovation. Nature. 2000, 405: 299-304. 10.1038/35012500.View ArticlePubMedGoogle Scholar
- Syvanen M: Cross-species gene transfer; implications for a new theory of evolution. J Theor Biol. 1985, 112: 333-343.View ArticlePubMedGoogle Scholar
- Hilario E, Gogarten JP: Horizontal transfer of ATPase genes--the tree of life becomes a net of life. Biosystems. 1993, 31: 111-119. 10.1016/0303-2647(93)90038-E.View ArticlePubMedGoogle Scholar
- Lawrence JG, Ochman H: Molecular archaeology of the Escherichia coli genome. Proc Natl Acad Sci U S A. 1998, 95: 9413-9417. 10.1073/pnas.95.16.9413.View ArticlePubMedPubMed CentralGoogle Scholar
- Aravind L, Tatusov RL, Wolf YI, Walker DR, Koonin EV: Evidence for massive gene exchange between archaeal and bacterial hyperthermophiles. Trends Genet. 1998, 14: 442-444. 10.1016/S0168-9525(98)01553-4.View ArticlePubMedGoogle Scholar
- Nelson KE, Clayton RA, Gill SR, Gwinn ML, Dodson RJ, Haft DH, Hickey EK, Peterson JD, Nelson WC, Ketchum KA, McDonald L, Utterback TR, Malek JA, Linher KD, Garrett MM, Stewart AM, Cotton MD, Pratt MS, Phillips CA, Richardson D, Heidelberg J, Sutton GG, Fleischmann RD, Eisen JA, Fraser CM, et al.: Evidence for lateral gene transfer between Archaea and bacteria from genome sequence of Thermotoga maritima. Nature. 1999, 399: 323-329. 10.1038/20601.View ArticlePubMedGoogle Scholar
- Perna NT, Plunkett G., 3rd, Burland V, Mau B, Glasner JD, Rose DJ, Mayhew GF, Evans PS, Gregor J, Kirkpatrick HA, Posfai G, Hackett J, Klink S, Boutin A, Shao Y, Miller L, Grotbeck EJ, Davis NW, Lim A, Dimalanta ET, Potamousis KD, Apodaca J, Anantharaman TS, Lin J, Yen G, Schwartz DC, Welch RA, Blattner FR: Genome sequence of enterohaemorrhagic Escherichia coli O157:H7. Nature. 2001, 409: 529-533. 10.1038/35054089.View ArticlePubMedGoogle Scholar
- Faguy DM, Doolittle WF: Horizontal transfer of catalase-peroxidase genes between archaea and pathogenic bacteria. Trends Genet. 2000, 16: 196-7. _00002007 _00002007. 10.1016/S0168-9525(00)02007-2.View ArticlePubMedGoogle Scholar
- Faguy DM: The controlled chaos of shifty pathogens. Curr Biol. 2000, 10: R498-501. 10.1016/S0960-9822(00)00558-3.View ArticlePubMedGoogle Scholar
- Koonin EV, Makarova KS, Aravind L: Horizontal gene transfer in prokaryotes: quantification and classification. Annu Rev Microbiol. 2001, 55: 709-742. 10.1146/annurev.micro.55.1.709.View ArticlePubMedPubMed CentralGoogle Scholar
- Doolittle WF: Phylogenetic classification and the universal tree. Science. 1999, 284: 2124-2129. 10.1126/science.284.5423.2124.View ArticlePubMedGoogle Scholar
- Doolittle WF: Uprooting the tree of life. Sci Am. 2000, 282: 90-95.View ArticlePubMedGoogle Scholar
- Levin BR, Bergstrom CT: Bacteria are different: observations, interpretations, speculations, and opinions about the mechanisms of adaptive evolution in prokaryotes. Proc Natl Acad Sci U S A. 2000, 97: 6981-6985. 10.1073/pnas.97.13.6981.View ArticlePubMedPubMed CentralGoogle Scholar
- Ragan MA: Detection of lateral gene transfer among microbial genomes. Curr Opin Genet Dev. 2001, 11: 620-626. 10.1016/S0959-437X(00)00244-6.View ArticlePubMedGoogle Scholar
- Lin CZ, Raskin L, Stahl DA: Microbial community structure in gastrointestinal tracts of domestic animals: Comparative analyses using rRNA-targeted oligonucleotide probes. Fems Microbiology Ecology. 1997, 22: 281-294. 10.1016/S0168-6496(97)00002-0.View ArticleGoogle Scholar
- Hancock DD, Rice DH, Herriott DE, Besser TE, Ebel ED, Carpenter LV: Effects of farm manure-handling practices on Escherichia coli O157 prevalence in cattle. Journal of Food Protection. 1997, 60: 363-366.Google Scholar
- Zillig W, Prangishvilli D, Schleper C, Elferink M, Holz I, Albers S, Janekovic D, Gotz D: Viruses, plasmids and other genetic elements of thermophilic and hyperthermophilic Archaea. FEMS Microbiol Rev. 1996, 18: 225-236. 10.1016/0168-6445(96)00014-9.View ArticlePubMedGoogle Scholar
- Bushman Frederic: Lateral DNA transfer : mechanisms and consequences. 2002, Cold Spring Harbor, NY, Cold Spring Harbor Laboratory Press, xiv, 448-Google Scholar
- Blattner FR, Plunkett G., 3rd, Bloch CA, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF, Gregor J, Davis NW, Kirkpatrick HA, Goeden MA, Rose DJ, Mau B, Shao Y: The complete genome sequence of Escherichia coli K-12. Science. 1997, 277: 1453-1474. 10.1126/science.277.5331.1453.View ArticlePubMedGoogle Scholar
- Hayashi T, Makino K, Ohnishi M, Kurokawa K, Ishii K, Yokoyama K, Han CG, Ohtsubo E, Nakayama K, Murata T, Tanaka M, Tobe T, Iida T, Takami H, Honda T, Sasakawa C, Ogasawara N, Yasunaga T, Kuhara S, Shiba T, Hattori M, Shinagawa H: Complete genome sequence of enterohemorrhagic Escherichia coli O157:H7 and genomic comparison with a laboratory strain K-12. DNA Res. 2001, 8: 11-22.View ArticlePubMedGoogle Scholar
- Welch RA, Burland V, Plunkett G., 3rd, Redford P, Roesch P, Rasko D, Buckles EL, Liou SR, Boutin A, Hackett J, Stroud D, Mayhew GF, Rose DJ, Zhou S, Schwartz DC, Perna NT, Mobley HL, Donnenberg MS, Blattner FR: Extensive mosaic structure revealed by the complete genome sequence of uropathogenic Escherichia coli. Proc Natl Acad Sci U S A. 2002, 99: 17020-17024. 10.1073/pnas.252529799.View ArticlePubMedPubMed CentralGoogle Scholar
- Bernal A, Ear U, Kyrpides N: Genomes OnLine Database (GOLD): a monitor of genome projects world-wide. Nucleic Acids Res. 2001, 29: 126-127. 10.1093/nar/29.1.126.View ArticlePubMedPubMed CentralGoogle Scholar
- Zhang XL, Morris C, Hackett J: Molecular cloning, nucleotide sequence, and function of a site-specific recombinase encoded in the major 'pathogenicity island' of Salmonella typhi. Gene. 1997, 202: 139-146. 10.1016/S0378-1119(97)00466-6.View ArticlePubMedGoogle Scholar
- Manca C, Paul S, Barry C. E., 3rd, Freedman VH, Kaplan G: Mycobacterium tuberculosis catalase and peroxidase activities and resistance to oxidative killing in human monocytes in vitro. Infect Immun. 1999, 67: 74-79.PubMedPubMed CentralGoogle Scholar
- Yu S, Chouchane S, Magliozzo RS: Characterization of the W321F mutant of Mycobacterium tuberculosis catalase-peroxidase KatG. Protein Sci. 2002, 11: 58-64. 10.1110/ps.ps.09902.View ArticlePubMedPubMed CentralGoogle Scholar
- Bandyopadhyay P, Steinman HM: Legionella pneumophila catalase-peroxidases: cloning of the katB gene and studies of KatB function. J Bacteriol. 1998, 180: 5369-5374.PubMedPubMed CentralGoogle Scholar
- Cianciotto NP: Pathogenicity of Legionella pneumophila. Int J Med Microbiol. 2001, 291: 331-343.View ArticlePubMedGoogle Scholar
- Bandyopadhyay P, Steinman HM: Catalase-peroxidases of Legionella pneumophila: cloning of the katA gene and studies of KatA function. J Bacteriol. 2000, 182: 6679-6686. 10.1128/JB.182.23.6679-6686.2000.View ArticlePubMedPubMed CentralGoogle Scholar
- Brunder W, Schmidt H, Karch H: KatP, a novel catalase-peroxidase encoded by the large plasmid of enterohaemorrhagic Escherichia coli O157:H7. Microbiology. 1996, 142: 3305-3315.View ArticlePubMedGoogle Scholar
- Stephan R, Ragettli S, Untermann F: Prevalence and characteristics of verotoxin-producing Escherichia coli (VTEC) in stool samples from asymptomatic human carriers working in the meat processing industry in Switzerland. J Appl Microbiol. 2000, 88: 335-341. 10.1046/j.1365-2672.2000.00965.x.View ArticlePubMedGoogle Scholar
- Burland V, Shao Y, Perna NT, Plunkett G, Sofia HJ, Blattner FR: The complete DNA sequence and analysis of the large virulence plasmid of Escherichia coli O157:H7. Nucleic Acids Res. 1998, 26: 4196-4204. 10.1093/nar/26.18.4196.View ArticlePubMedPubMed CentralGoogle Scholar
- Tatusov RL, Koonin EV, Lipman DJ: A genomic perspective on protein families. Science. 1997, 278: 631-637. 10.1126/science.278.5338.631.View ArticlePubMedGoogle Scholar
- Tatusov RL, Natale DA, Garkavtsev IV, Tatusova TA, Shankavaram UT, Rao BS, Kiryutin B, Galperin MY, Fedorova ND, Koonin EV: The COG database: new developments in phylogenetic classification of proteins from complete genomes. Nucleic Acids Res. 2001, 29: 22-28. 10.1093/nar/29.1.22.View ArticlePubMedPubMed CentralGoogle Scholar
- Jakubovics NS, Smith AW, Jenkinson HF: Oxidative stress tolerance is manganese (Mn(2+)) regulated in Streptococcus gordonii. Microbiology. 2002, 148: 3255-3263.View ArticlePubMedGoogle Scholar
- Harb OS, Abu Kwaik Y: Essential role for the Legionella pneumophila rep helicase homologue in intracellular infection of mammalian cells. Infect Immun. 2000, 68: 6970-6978. 10.1128/IAI.68.12.6970-6978.2000.View ArticlePubMedPubMed CentralGoogle Scholar
- Faguy DM, Doolittle WF: Lessons from the Aeropyrum pernix genome. Curr Biol. 1999, 9: R883-6. 10.1016/S0960-9822(00)80074-3.View ArticlePubMedGoogle Scholar
- Logsdon JM, Faguy DM: Thermotoga heats up lateral gene transfer. Curr Biol. 1999, 9: R747-51. 10.1016/S0960-9822(99)80474-6.View ArticlePubMedGoogle Scholar
- Kyrpides NC, Ouzounis CA: Whole-genome sequence annotation: 'Going wrong with confidence'. Mol Microbiol. 1999, 32: 886-887. 10.1046/j.1365-2958.1999.01380.x.View ArticlePubMedGoogle Scholar
- Eisen JA: Horizontal gene transfer among microbial genomes: new insights from complete genome analysis. Curr Opin Genet Dev. 2000, 10: 606-611. 10.1016/S0959-437X(00)00143-X.View ArticlePubMedGoogle Scholar
- Wang B: Limitations of compositional approach to identifying horizontally transferred genes. J Mol Evol. 2001, 53: 244-250. 10.1007/s002390010214.View ArticlePubMedGoogle Scholar
- Lawrence JG, Ochman H: Reconciling the many faces of lateral gene transfer. Trends Microbiol. 2002, 10: 1-4. 10.1016/S0966-842X(01)02282-X.View ArticlePubMedGoogle Scholar
- Parkhill J, Wren BW, Thomson NR, Titball RW, Holden MT, Prentice MB, Sebaihia M, James KD, Churcher C, Mungall KL, Baker S, Basham D, Bentley SD, Brooks K, Cerdeno-Tarraga AM, Chillingworth T, Cronin A, Davies RM, Davis P, Dougan G, Feltwell T, Hamlin N, Holroyd S, Jagels K, Karlyshev AV, Leather S, Moule S, Oyston PC, Quail M, Rutherford K, Simmonds M, Skelton J, Stevens K, Whitehead S, Barrell BG: Genome sequence of Yersinia pestis, the causative agent of plague. Nature. 2001, 413: 523-527. 10.1038/35097083.View ArticlePubMedGoogle Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2334/3/13/prepub
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