Comprehensive analysis of chromosomal mobile genetic elements in the gut microbiome reveals phylum-level niche-adaptive gene pools


Autoři: Xiaofang Jiang aff001;  Andrew Brantley Hall aff002;  Ramnik J. Xavier aff001;  Eric J. Alm aff001
Působiště autorů: Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA, United States of America aff001;  Broad Institute of MIT and Harvard, Cambridge, MA, United States of America aff002;  Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America aff003;  Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America aff004;  MIT Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States of America aff005
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0223680

Souhrn

Mobile genetic elements (MGEs) drive extensive horizontal transfer in the gut microbiome. This transfer could benefit human health by conferring new metabolic capabilities to commensal microbes, or it could threaten human health by spreading antibiotic resistance genes to pathogens. Despite their biological importance and medical relevance, MGEs from the gut microbiome have not been systematically characterized. Here, we present a comprehensive analysis of chromosomal MGEs in the gut microbiome using a method that enables the identification of the mobilizable unit of MGEs. We curated a database of 5,219 putative MGEs encompassing seven MGE classes called ImmeDB. We observed that many MGEs carry genes that could confer an adaptive advantage to the gut environment including gene families involved in antibiotic resistance, bile salt detoxification, mucus degradation, capsular polysaccharide biosynthesis, polysaccharide utilization, and sporulation. We find that antibiotic resistance genes are more likely to be spread by conjugation via integrative conjugative elements or integrative mobilizable elements than transduction via prophages. Horizontal transfer of MGEs is extensive within phyla but rare across phyla, supporting phylum level niche-adaptive gene pools in the gut microbiome. ImmeDB will be a valuable resource for future studies on the gut microbiome and MGE communities.

Klíčová slova:

Antibiotic resistance – Comparative genomics – Metagenomics – Microbiome – Polysaccharides – Serine – Transposable elements – Tyrosine


Zdroje

1. Soucy SM, Huang J, Gogarten JP. Horizontal gene transfer: building the web of life. Nat Rev Genet. 2015;16: 472–482. doi: 10.1038/nrg3962 26184597

2. Smillie CS, Smith MB, Friedman J, Cordero OX, David LA, Alm EJ. Ecology drives a global network of gene exchange connecting the human microbiome. Nature. 2011;480: 241–244. doi: 10.1038/nature10571 22037308

3. Brito IL, Yilmaz S, Huang K, Xu L, Jupiter SD, Jenkins AP, et al. Mobile genes in the human microbiome are structured from global to individual scales. Nature. Nature Research; 2016;535: 435–439.

4. Huddleston JR. Horizontal gene transfer in the human gastrointestinal tract: potential spread of antibiotic resistance genes. Infect Drug Resist. 2014;7: 167–176. doi: 10.2147/IDR.S48820 25018641

5. Roberts AP, Mullany P. Oral biofilms: a reservoir of transferable, bacterial, antimicrobial resistance. Expert Rev Anti Infect Ther. 2010;8: 1441–1450. doi: 10.1586/eri.10.106 21133668

6. Hehemann J-H, Correc G, Barbeyron T, Helbert W, Czjzek M, Michel G. Transfer of carbohydrate-active enzymes from marine bacteria to Japanese gut microbiota. Nature. 2010;464: 908–912. doi: 10.1038/nature08937 20376150

7. Krupovic M, Prangishvili D, Hendrix RW, Bamford DH. Genomics of bacterial and archaeal viruses: dynamics within the prokaryotic virosphere. Microbiol Mol Biol Rev. 2011;75: 610–635. doi: 10.1128/MMBR.00011-11 22126996

8. Lambowitz AM, Zimmerly S. Group II introns: mobile ribozymes that invade DNA. Cold Spring Harb Perspect Biol. 2011;3: a003616. doi: 10.1101/cshperspect.a003616 20463000

9. Treangen TJ, Rocha EPC. Horizontal transfer, not duplication, drives the expansion of protein families in prokaryotes. PLoS Genet. 2011;7: e1001284. doi: 10.1371/journal.pgen.1001284 21298028

10. Hacker J, Carniel E. Ecological fitness, genomic islands and bacterial pathogenicity. A Darwinian view of the evolution of microbes. EMBO Rep. EMBO Press; 2001;2: 376–381.

11. Wozniak RAF, Waldor MK. Integrative and conjugative elements: mosaic mobile genetic elements enabling dynamic lateral gene flow. Nat Rev Microbiol. 2010;8: 552–563. doi: 10.1038/nrmicro2382 20601965

12. Johnson CM, Grossman AD. Integrative and Conjugative Elements (ICEs): What They Do and How They Work. Annu Rev Genet. 2015;49: 577–601. doi: 10.1146/annurev-genet-112414-055018 26473380

13. Bellanger X, Payot S, Leblond-Bourget N, Guédon G. Conjugative and mobilizable genomic islands in bacteria: evolution and diversity. FEMS Microbiol Rev. 2014;38: 720–760. doi: 10.1111/1574-6976.12058 24372381

14. Ravenhall M, Škunca N, Lassalle F, Dessimoz C. Inferring horizontal gene transfer. PLoS Comput Biol. 2015;11: e1004095. doi: 10.1371/journal.pcbi.1004095 26020646

15. Hoen DR, Hickey G, Bourque G, Casacuberta J, Cordaux R, Feschotte C, et al. A call for benchmarking transposable element annotation methods. Mob DNA. 2015;6: 13. doi: 10.1186/s13100-015-0044-6 26244060

16. Arndt D, Grant JR, Marcu A, Sajed T, Pon A, Liang Y, et al. PHASTER: a better, faster version of the PHAST phage search tool. Nucleic Acids Res. 2016;44: W16–21. doi: 10.1093/nar/gkw387 27141966

17. Siguier P, Perochon J, Lestrade L, Mahillon J, Chandler M. ISfinder: the reference centre for bacterial insertion sequences. Nucleic Acids Res. 2006;34: D32–6. doi: 10.1093/nar/gkj014 16381877

18. Bi D, Xu Z, Harrison EM, Tai C, Wei Y, He X, et al. ICEberg: a web-based resource for integrative and conjugative elements found in Bacteria. Nucleic Acids Res. 2012;40: D621–6. doi: 10.1093/nar/gkr846 22009673

19. Leplae R, Lima-Mendez G, Toussaint A. ACLAME: a CLAssification of Mobile genetic Elements, update 2010. Nucleic Acids Res. 2010;38: D57–61. doi: 10.1093/nar/gkp938 19933762

20. Belda-Ferre P, Cabrera-Rubio R, Moya A, Mira A. Mining virulence genes using metagenomics. PLoS One. 2011;6: e24975. doi: 10.1371/journal.pone.0024975 22039404

21. Trappe K, Marschall T, Renard BY. Detecting horizontal gene transfer by mapping sequencing reads across species boundaries. Bioinformatics. 2016;32: i595–i604. doi: 10.1093/bioinformatics/btw423 27587679

22. Parks DH, Imelfort M, Skennerton CT, Hugenholtz P, Tyson GW. CheckM: assessing the quality of microbial genomes recovered from isolates, single cells, and metagenomes. Genome Res. 2015;25: 1043–1055. doi: 10.1101/gr.186072.114 25977477

23. Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature. 2012;486: 207–214. doi: 10.1038/nature11234 22699609

24. Ondov BD, Treangen TJ, Melsted P, Mallonee AB, Bergman NH, Koren S, et al. Mash: fast genome and metagenome distance estimation using MinHash. Genome Biol. 2016;17: 132. doi: 10.1186/s13059-016-0997-x 27323842

25. Li H, Durbin R. Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinformatics. Oxford University Press; 2009;25: 1754–1760.

26. Hyatt D, Chen G-L, Locascio PF, Land ML, Larimer FW, Hauser LJ. Prodigal: prokaryotic gene recognition and translation initiation site identification. BMC Bioinformatics. 2010;11: 119. doi: 10.1186/1471-2105-11-119 20211023

27. Jones P, Binns D, Chang H-Y, Fraser M, Li W, McAnulla C, et al. InterProScan 5: genome-scale protein function classification. Bioinformatics. 2014;30: 1236–1240. doi: 10.1093/bioinformatics/btu031 24451626

28. Fouts DE. Phage_Finder: automated identification and classification of prophage regions in complete bacterial genome sequences. Nucleic Acids Res. 2006;34: 5839–5851. doi: 10.1093/nar/gkl732 17062630

29. Abby SS, Cury J, Guglielmini J, Néron B, Touchon M, Rocha EPC. Identification of protein secretion systems in bacterial genomes. Sci Rep. 2016;6: 23080. doi: 10.1038/srep23080 26979785

30. Cury J, Touchon M, Rocha EPC. Integrative and conjugative elements and their hosts: composition, distribution and organization. Nucleic Acids Res. 2017;45: 8943–8956. doi: 10.1093/nar/gkx607 28911112

31. Kurtz S, Phillippy A, Delcher AL, Smoot M, Shumway M, Antonescu C, et al. Versatile and open software for comparing large genomes. Genome Biol. 2004;5: R12. doi: 10.1186/gb-2004-5-2-r12 14759262

32. Katoh K, Standley DM. MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol Biol Evol. 2013;30: 772–780. doi: 10.1093/molbev/mst010 23329690

33. Capella-Gutiérrez S, Silla-Martínez JM, Gabaldón T. trimAl: a tool for automated alignment trimming in large-scale phylogenetic analyses. Bioinformatics. 2009;25: 1972–1973. doi: 10.1093/bioinformatics/btp348 19505945

34. Stamatakis A. RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies. Bioinformatics. 2014;30: 1312–1313. doi: 10.1093/bioinformatics/btu033 24451623

35. Revell LJ. Phytools: Phylogenetic tools or comparative biology (and other things). 2011.

36. Johnson LS, Eddy SR, Portugaly E. Hidden Markov model speed heuristic and iterative HMM search procedure. BMC Bioinformatics. 2010;11: 431. doi: 10.1186/1471-2105-11-431 20718988

37. Gibson MK, Forsberg KJ, Dantas G. Improved annotation of antibiotic resistance determinants reveals microbial resistomes cluster by ecology. ISME J. 2015;9: 207–216. doi: 10.1038/ismej.2014.106 25003965

38. Beissbarth T, Speed TP. GOstat: find statistically overrepresented Gene Ontologies within a group of genes. Bioinformatics. 2004;20: 1464–1465. doi: 10.1093/bioinformatics/bth088 14962934

39. Yu G, Wang L-G, Han Y, He Q-Y. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS. 2012;16: 284–287. doi: 10.1089/omi.2011.0118 22455463

40. Guglielmini J, Néron B, Abby SS, Garcillán-Barcia MP, de la Cruz F, Rocha EPC. Key components of the eight classes of type IV secretion systems involved in bacterial conjugation or protein secretion. Nucleic Acids Res. 2014;42: 5715–5727. doi: 10.1093/nar/gku194 24623814

41. Guglielmini J, de la Cruz F, Rocha EPC. Evolution of conjugation and type IV secretion systems. Mol Biol Evol. 2013;30: 315–331. doi: 10.1093/molbev/mss221 22977114

42. Rankin DJ, Rocha EPC, Brown SP. What traits are carried on mobile genetic elements, and why? Heredity. 2011;106: 1–10. doi: 10.1038/hdy.2010.24 20332804

43. Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Michael Cherry J, et al. Gene Ontology: tool for the unification of biology. Nat Genet. Nature Publishing Group; 2000;25: 25–29. doi: 10.1038/75556 10802651

44. Finn RD, Bateman A, Clements J, Coggill P, Eberhardt RY, Eddy SR, et al. Pfam: the protein families database. Nucleic Acids Res. 2014;42: D222–30. doi: 10.1093/nar/gkt1223 24288371

45. Connelly S, Bristol JA, Hubert S, Subramanian P, Hasan NA, Colwell RR, et al. SYN-004 (ribaxamase), an Oral Beta-Lactamase, Mitigates Antibiotic-Mediated Dysbiosis in a Porcine Gut Microbiome Model. J Appl Microbiol. 2017; doi: 10.1111/jam.13432 28245091

46. Volkova VV, Lu Z, Besser T, Gröhn YT. Modeling the infection dynamics of bacteriophages in enteric Escherichia coli: estimating the contribution of transduction to antimicrobial gene spread. Appl Environ Microbiol. 2014;80: 4350–4362. doi: 10.1128/AEM.00446-14 24814786

47. Enault F, Briet A, Bouteille L, Roux S, Sullivan MB, Petit M-A. Phages rarely encode antibiotic resistance genes: a cautionary tale for virome analyses. ISME J. 2017;11: 237–247. doi: 10.1038/ismej.2016.90 27326545

48. Shoemaker NB, Vlamakis H, Hayes K, Salyers AA. Evidence for extensive resistance gene transfer among Bacteroides spp. and among Bacteroides and other genera in the human colon. Appl Environ Microbiol. 2001;67: 561–568. doi: 10.1128/AEM.67.2.561-568.2001 11157217

49. Devlin AS, Fischbach MA. A biosynthetic pathway for a prominent class of microbiota-derived bile acids. Nat Chem Biol. 2015;11: 685–690. doi: 10.1038/nchembio.1864 26192599

50. Begley M, Gahan CGM, Hill C. The interaction between bacteria and bile. FEMS Microbiol Rev. 2005;29: 625–651. doi: 10.1016/j.femsre.2004.09.003 16102595

51. Jones BV, Begley M, Hill C, Gahan CGM, Marchesi JR. Functional and comparative metagenomic analysis of bile salt hydrolase activity in the human gut microbiome. Proc Natl Acad Sci U S A. 2008;105: 13580–13585. doi: 10.1073/pnas.0804437105 18757757

52. Johansson MEV, Phillipson M, Petersson J, Velcich A, Holm L, Hansson GC. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Proceedings of the National Academy of Sciences. 2008;105: 15064–15069.

53. Johansson MEV, Larsson JMH, Hansson GC. The two mucus layers of colon are organized by the MUC2 mucin, whereas the outer layer is a legislator of host-microbial interactions. Proc Natl Acad Sci U S A. 2011;108 Suppl 1: 4659–4665.

54. Tailford LE, Crost EH, Kavanaugh D, Juge N. Mucin glycan foraging in the human gut microbiome. Front Genet. 2015;6: 81. doi: 10.3389/fgene.2015.00081 25852737

55. Li H, Limenitakis JP, Fuhrer T, Geuking MB, Lawson MA, Wyss M, et al. The outer mucus layer hosts a distinct intestinal microbial niche. Nat Commun. 2015;6: 8292. doi: 10.1038/ncomms9292 26392213

56. Lombard V, Golaconda Ramulu H, Drula E, Coutinho PM, Henrissat B. The carbohydrate-active enzymes database (CAZy) in 2013. Nucleic Acids Res. 2014;42: D490–5. doi: 10.1093/nar/gkt1178 24270786

57. Koropatkin NM, Cameron EA, Martens EC. How glycan metabolism shapes the human gut microbiota. Nat Rev Microbiol. 2012;10: 323–335. doi: 10.1038/nrmicro2746 22491358

58. Ravcheev DA, Godzik A, Osterman AL, Rodionov DA. Polysaccharides utilization in human gut bacterium Bacteroides thetaiotaomicron: comparative genomics reconstruction of metabolic and regulatory networks. BMC Genomics. 2013;14: 873. doi: 10.1186/1471-2164-14-873 24330590

59. Comstock LE, Coyne MJ, Tzianabos AO, Pantosti A, Onderdonk AB, Kasper DL. Analysis of a capsular polysaccharide biosynthesis locus of Bacteroides fragilis. Infect Immun. 1999;67: 3525–3532. 10377135

60. Zitomersky NL, Coyne MJ, Comstock LE. Longitudinal analysis of the prevalence, maintenance, and IgA response to species of the order Bacteroidales in the human gut. Infect Immun. 2011;79: 2012–2020. doi: 10.1128/IAI.01348-10 21402766

61. Wu M, McNulty NP, Rodionov DA, Khoroshkin MS, Griffin NW, Cheng J, et al. Genetic determinants of in vivo fitness and diet responsiveness in multiple human gut Bacteroides. Science. 2015;350: aac5992. doi: 10.1126/science.aac5992 26430127

62. Patrick S, Blakely GW, Houston S, Moore J, Abratt VR, Bertalan M, et al. Twenty-eight divergent polysaccharide loci specifying within- and amongst-strain capsule diversity in three strains of Bacteroides fragilis. Microbiology. 2010;156: 3255–3269. doi: 10.1099/mic.0.042978-0 20829291

63. Coyne MJ, Chatzidaki-Livanis M, Paoletti LC, Comstock LE. Role of glycan synthesis in colonization of the mammalian gut by the bacterial symbiont Bacteroides fragilis. Proceedings of the National Academy of Sciences. 2008;105: 13099–13104.

64. Xu J, Mahowald MA, Ley RE, Lozupone CA, Hamady M, Martens EC, et al. Evolution of symbiotic bacteria in the distal human intestine. PLoS Biol. 2007;5: e156. doi: 10.1371/journal.pbio.0050156 17579514

65. Albenberg L, Esipova TV, Judge CP, Bittinger K, Chen J, Laughlin A, et al. Correlation between intraluminal oxygen gradient and radial partitioning of intestinal microbiota. Gastroenterology. 2014;147: 1055–63.e8. doi: 10.1053/j.gastro.2014.07.020 25046162

66. Duncan SH, Hold GL, Harmsen HJM, Stewart CS, Flint HJ. Growth requirements and fermentation products of Fusobacterium prausnitzii, and a proposal to reclassify it as Faecalibacterium prausnitzii gen. nov., comb. nov. Int J Syst Evol Microbiol. 2002;52: 2141–2146. doi: 10.1099/00207713-52-6-2141 12508881

67. Browne HP, Forster SC, Anonye BO, Kumar N, Anne Neville B, Stares MD, et al. Culturing of “unculturable” human microbiota reveals novel taxa and extensive sporulation. Nature. Nature Research; 2016;533: 543–546.

68. Berendsen EM, Boekhorst J, Kuipers OP, Wells-Bennik MHJ. A mobile genetic element profoundly increases heat resistance of bacterial spores. ISME J. 2016;10: 2633–2642. doi: 10.1038/ismej.2016.59 27105070

69. Sommer MOA, Church GM, Dantas G. The human microbiome harbors a diverse reservoir of antibiotic resistance genes. Virulence. 2010;1: 299–303. doi: 10.4161/viru.1.4.12010 21178459

70. Whittle G, Hund BD, Shoemaker NB, Salyers AA. Characterization of the 13-kilobase ermF region of the Bacteroides conjugative transposon CTnDOT. Appl Environ Microbiol. 2001;67: 3488–3495. doi: 10.1128/AEM.67.8.3488-3495.2001 11472924

71. Garnier F, Taourit S, Glaser P, Courvalin P, Galimand M. Characterization of transposon Tn1549, conferring VanB-type resistance in Enterococcus spp. Microbiology. 2000;146 (Pt 6): 1481–1489.

72. Napolitano MG, Almagro-Moreno S, Boyd EF. Dichotomy in the evolution of pathogenicity island and bacteriophage encoded integrases from pathogenic Escherichia coli strains. Infect Genet Evol. 2011;11: 423–436. doi: 10.1016/j.meegid.2010.12.003 21147268

73. Van Houdt R, Leplae R, Lima-Mendez G, Mergeay M, Toussaint A. Towards a more accurate annotation of tyrosine-based site-specific recombinases in bacterial genomes. Mob DNA. 2012;3: 6. doi: 10.1186/1759-8753-3-6 22502997

74. Whittle G, Hamburger N, Shoemaker NB, Salyers AA. A bacteroides conjugative transposon, CTnERL, can transfer a portion of itself by conjugation without excising from the chromosome. J Bacteriol. 2006;188: 1169–1174. doi: 10.1128/JB.188.3.1169-1174.2006 16428422

75. Liu M, Li X, Xie Y, Bi D, Sun J, Li J, et al. ICEberg 2.0: an updated database of bacterial integrative and conjugative elements. Nucleic Acids Res. 2019;47: D660–D665. doi: 10.1093/nar/gky1123 30407568

76. Rizzatti G, Lopetuso LR, Gibiino G, Binda C, Gasbarrini A. Proteobacteria: A Common Factor in Human Diseases [Internet]. BioMed Research International. 2017. pp. 1–7. doi: 10.1155/2017/9351507 29230419

77. Truong DT, Franzosa EA, Tickle TL, Scholz M, Weingart G, Pasolli E, et al. MetaPhlAn2 for enhanced metagenomic taxonomic profiling. Nat Methods. 2015;12: 902–903. doi: 10.1038/nmeth.3589 26418763

78. Wood DE, Salzberg SL. Kraken: ultrafast metagenomic sequence classification using exact alignments. Genome Biol. 2014;15: R46. doi: 10.1186/gb-2014-15-3-r46 24580807

79. Ounit R, Wanamaker S, Close TJ, Lonardi S. CLARK: fast and accurate classification of metagenomic and genomic sequences using discriminative k-mers. BMC Genomics. 2015;16: 236. doi: 10.1186/s12864-015-1419-2 25879410

80. Ahn T-H, Chai J, Pan C. Sigma: strain-level inference of genomes from metagenomic analysis for biosurveillance. Bioinformatics. 2015;31: 170–177. doi: 10.1093/bioinformatics/btu641 25266224

81. Luo C, Knight R, Siljander H, Knip M, Xavier RJ, Gevers D. ConStrains identifies microbial strains in metagenomic datasets. Nat Biotechnol. 2015;33: 1045–1052. doi: 10.1038/nbt.3319 26344404

82. Greenblum S, Carr R, Borenstein E. Extensive strain-level copy-number variation across human gut microbiome species. Cell. 2015;160: 583–594. doi: 10.1016/j.cell.2014.12.038 25640238

83. Nayfach S, Rodriguez-Mueller B, Garud N, Pollard KS. An integrated metagenomics pipeline for strain profiling reveals novel patterns of bacterial transmission and biogeography. Genome Res. 2016;26: 1612–1625. doi: 10.1101/gr.201863.115 27803195

84. Smit A, Hubley R, Green P. RepeatMasker Open-4.0. 2013–2015. Institute for Systems Biology http://repeatmasker org. 2015;

85. Bao W, Kojima KK, Kohany O. Repbase Update, a database of repetitive elements in eukaryotic genomes. Mob DNA. 2015;6: 11. doi: 10.1186/s13100-015-0041-9 26045719

86. Antibiotic / Antimicrobial Resistance | CDC [Internet]. [cited 14 Jun 2017]. Available: https://www.cdc.gov/drugresistance/index.html

87. Caballero S, Kim S, Carter RA, Leiner IM, Sušac B, Miller L, et al. Cooperating Commensals Restore Colonization Resistance to Vancomycin-Resistant Enterococcus faecium. Cell Host Microbe. 2017;21: 592–602.e4. doi: 10.1016/j.chom.2017.04.002 28494240

88. Mimee M, Tucker AC, Voigt CA, Lu TK. Programming a Human Commensal Bacterium, Bacteroides thetaiotaomicron, to Sense and Respond to Stimuli in the Murine Gut Microbiota. Cell Syst. 2015;1: 62–71. doi: 10.1016/j.cels.2015.06.001 26918244

89. Liu Y-J, Zhang J, Cui G-Z, Cui Q. Current progress of targetron technology: development, improvement and application in metabolic engineering. Biotechnol J. 2015;10: 855–865. doi: 10.1002/biot.201400716 25735546


Článek vyšel v časopise

PLOS One


2019 Číslo 12