Mobile Type VI secretion system loci of the gut Bacteroidales display extensive intra-ecosystem transfer, multi-species spread and geographical clustering
Autoři:
Leonor García-Bayona aff001; Michael J. Coyne aff001; Laurie E. Comstock aff001
Působiště autorů:
Division of Infectious Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
aff001
Vyšlo v časopise:
Mobile Type VI secretion system loci of the gut Bacteroidales display extensive intra-ecosystem transfer, multi-species spread and geographical clustering. PLoS Genet 17(4): e1009541. doi:10.1371/journal.pgen.1009541
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1009541
Souhrn
The human gut microbiota is a dense microbial ecosystem with extensive opportunities for bacterial contact-dependent processes such as conjugation and Type VI secretion system (T6SS)-dependent antagonism. In the gut Bacteroidales, two distinct genetic architectures of T6SS loci, GA1 and GA2, are contained on Integrative and Conjugative Elements (ICE). Despite intense interest in the T6SSs of the gut Bacteroidales, there is only a superficial understanding of their evolutionary patterns, and of their dissemination among Bacteroidales species in human gut communities. Here, we combine extensive genomic and metagenomic analyses to better understand their ecological and evolutionary dynamics. We identify new genetic subtypes, document extensive intrapersonal transfer of these ICE to Bacteroidales species within human gut microbiomes, and most importantly, reveal frequent population fixation of these newly armed strains in multiple species within a person. We further show the distribution of each of the distinct T6SSs in human populations and show there is geographical clustering. We reveal that the GA1 T6SS ICE integrates at a minimal recombination site leading to their integration throughout genomes and their frequent interruption of genes, whereas the GA2 T6SS ICE integrate at one of three different tRNA genes. The exclusion of concurrent GA1 and GA2 T6SSs in individual strains is associated with intact T6SS loci and with an ICE-encoded gene. By performing a comprehensive analysis of mobile genetic elements (MGE) in co-resident Bacteroidales species in numerous human gut communities, we identify 74 MGE that transferred to multiple Bacteroidales species within individual gut microbiomes. We further show that only three other MGE demonstrate multi-species spread in human gut microbiomes to the degree demonstrated by the GA1 and GA2 ICE. These data underscore the ubiquity and dissemination of mobile T6SS loci within Bacteroidales communities and across human populations.
Klíčová slova:
Bacteroides – Genetic loci – Genome analysis – Genomics – Gut bacteria – Metagenomics – Mobile genetic elements – Secretion systems
Zdroje
1. Garcia-Bayona L, Comstock LE. Bacterial antagonism in host-associated microbial communities. Science. 2018;361(6408). doi: 10.1126/science.aat2456 30237322.
2. Wang J, Brodmann M, Basler M. Assembly and Subcellular Localization of Bacterial Type VI Secretion Systems. Annu Rev Microbiol. 2019;73:621–38. doi: 10.1146/annurev-micro-020518-115420 31226022.
3. Coyne M, Roelofs KG, Comstock LE. Type VI secretion systems of human gut Bacteroidales segregate into three genetic architectures, two of which are contained on mobile genetic elements. BMC Genomics. 2016;17(58). doi: 10.1186/s12864-016-2377-z 26768901
4. Chatzidaki-Livanis M, Geva-Zatorsky N, Comstock LE. Bacteroides fragilis type VI secretion systems use novel effector and immunity proteins to antagonize human gut Bacteroidales species. Proc Natl Acad Sci U S A. 2016;113(13):3627–32. doi: 10.1073/pnas.1522510113 26951680.
5. Wexler AG, Bao Y, Whitney JC, Bobay LM, Xavier JB, Schofield WB, et al. Human symbionts inject and neutralize antibacterial toxins to persist in the gut. Proc Natl Acad Sci U S A. 2016;113(13):3639–44. doi: 10.1073/pnas.1525637113 26957597.
6. Hecht AL, Casterline BW, Earley ZM, Goo YA, Goodlett DR, Bubeck Wardenburg J. Strain competition restricts colonization of an enteric pathogen and prevents colitis. EMBO reports. 2016;17(9):1281–91. doi: 10.15252/embr.201642282 27432285; PubMed Central PMCID: PMC5007561.
7. Verster AJ, Ross BD, Radey MC, Bao Y, Goodman AL, Mougous JD, et al. The Landscape of Type VI Secretion across Human Gut Microbiomes Reveals Its Role in Community Composition. Cell Host Microbe. 2017;22(3):411–9 e4. doi: 10.1016/j.chom.2017.08.010 28910638; PubMed Central PMCID: PMC5679258.
8. Marasini D, Karki AB, Bryant JM, Sheaff RJ, Fakhr MK. Molecular characterization of megaplasmids encoding the type VI secretion system in Campylobacter jejuni isolated from chicken livers and gizzards. Sci Rep. 2020;10(1):12514. doi: 10.1038/s41598-020-69155-z 32719325; PubMed Central PMCID: PMC7385129.
9. Ross BD, Verster AJ, Radey MC, Schmidtke DT, Pope CE, Hoffman LR, et al. Human gut bacteria contain acquired interbacterial defence systems. Nature. 2019;575(7781):224–8. doi: 10.1038/s41586-019-1708-z 31666699; PubMed Central PMCID: PMC6938237.
10. Santoriello FJ, Michel L, Unterweger D, Pukatzki S. Pandemic Vibrio cholerae shuts down site-specific recombination to retain an interbacterial defence mechanism. Nature Comm. 2020;11(1):6246. doi: 10.1038/s41467-020-20012-7 33288753; PubMed Central PMCID: PMC7721734.
11. Coyne M, Zitomersky N, McGuire A, Earl A, Comstock L. Evidence of extensive DNA transfer between Bacteroidales species within the human gut. mBio. 2014;5(3):e01305-14–e-14. doi: 10.1128/mBio.01305-14 24939888
12. Garud NR, Pollard KS. Population Genetics in the Human Microbiome. Trends Genet. 2020;36(1):53–67. Epub 2019/11/30. doi: 10.1016/j.tig.2019.10.010 31780057.
13. Coyne MJ, Roelofs KG, Comstock LE. Type VI secretion systems of human gut Bacteroidales segregate into three genetic architectures, two of which are contained on mobile genetic elements. BMC Genomics. 2016;17(1):1–21. doi: 10.1186/s12864-016-2377-z 26768901
14. 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(5):2012–20. Epub 2011/03/16. IAI.01348-10 [pii] 10.1128/IAI.01348-10. doi: 10.1128/IAI.01348-10 21402766
15. Poyet M, Groussin M, Gibbons SM, Avila-Pacheco J, Jiang X, Kearney SM, et al. A library of human gut bacterial isolates paired with longitudinal multiomics data enables mechanistic microbiome research. Nat Med. 2019;25(9):1442–52. doi: 10.1038/s41591-019-0559-3 31477907.
16. Zou Y, Xue W, Luo G, Deng Z, Qin P, Guo R, et al. 1,520 reference genomes from cultivated human gut bacteria enable functional microbiome analyses. Nature Biotechnol. 2019;37(2):179–85. doi: 10.1038/s41587-018-0008-8 30718868; PubMed Central PMCID: PMC6784896.
17. Browne HP, Forster SC, Anonye BO, Kumar N, Neville BA, Stares MD, et al. Culturing of ’unculturable’ human microbiota reveals novel taxa and extensive sporulation. Nature. 2016;533(7604):543–6. doi: 10.1038/nature17645 27144353; PubMed Central PMCID: PMC4890681.
18. Groussin M, Poyet M, Sistiaga A, Kearney SM, Moniz K, Noel M, et al. Elevated rates of horizontal gene transfer in the industrialized human microbiome. Cell. 2021; 184(8):2053–2067.e18. doi: 10.1016/j.cell.2021.02.052 33794144.
19. Waters JL, Salyers AA. Regulation of CTnDOT conjugative transfer is a complex and highly coordinated series of events. mBio. 2013;4(6):e00569–13. doi: 10.1128/mBio.00569-13 24169574; PubMed Central PMCID: PMC3809561.
20. Wesslund NA, Wang GR, Song B, Shoemaker NB, Salyers AA. Integration and excision of a newly discovered bacteroides conjugative transposon, CTnBST. J Bacteriol. 2007;189(3):1072–82. doi: 10.1128/JB.01064-06 17122349; PubMed Central PMCID: PMC1797293.
21. Wang GR, Shoemaker NB, Jeters RT, Salyers AA. CTn12256, a chimeric Bacteroides conjugative transposon that consists of two independently active mobile elements. Plasmid. 2011;66(2):93–105. doi: 10.1016/j.plasmid.2011.06.003 21777612.
22. Hehemann JH, Kelly AG, Pudlo NA, Martens EC, Boraston AB. Bacteria of the human gut microbiome catabolize red seaweed glycans with carbohydrate-active enzyme updates from extrinsic microbes. Proc Natl Acad Sci U S A. 2012;109(48):19786–91. doi: 10.1073/pnas.1211002109 23150581; PubMed Central PMCID: PMC3511707.
23. Wood MM, Gardner JF. The Integration and Excision of CTnDOT. Microbiol. Spectrum. 2015;3(2):MDNA3-0020-2014. doi: 10.1128/microbiolspec.MDNA3-0020-2014 26104696; PubMed Central PMCID: PMC4480416.
24. Avello M, Davis KP, Grossman AD. Identification, characterization and benefits of an exclusion system in an integrative and conjugative element of Bacillus subtilis. Mol Microbiol. 2019;112(4):1066–82. doi: 10.1111/mmi.14359 31361051; PubMed Central PMCID: PMC6827876.
25. Di Venanzio G, Moon KH, Weber BS, Lopez J, Ly PM, Potter RF, et al. Multidrug-resistant plasmids repress chromosomally encoded T6SS to enable their dissemination. Proc Natl Acad Sci U S A. 2019;116(4):1378–83. doi: 10.1073/pnas.1812557116 30626645; PubMed Central PMCID: PMC6347727.
26. Schwarz FW, Toth J, van Aelst K, Cui G, Clausing S, Szczelkun MD, et al. The helicase-like domains of type III restriction enzymes trigger long-range diffusion along DNA. Science. 2013;340(6130):353–6. doi: 10.1126/science.1231122 23599494; PubMed Central PMCID: PMC3646237.
27. Ofir G, Melamed S, Sberro H, Mukamel Z, Silverman S, Yaakov G, et al. DISARM is a widespread bacterial defence system with broad anti-phage activities. Nature Microbiol. 2018;3(1):90–8. doi: 10.1038/s41564-017-0051-0 29085076; PubMed Central PMCID: PMC5739279.
28. Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, et al. Enterotypes of the human gut microbiome. Nature. 2011;473(7346):174–80. doi: 10.1038/nature09944 21508958; PubMed Central PMCID: PMC3728647.
29. Costea PI, Hildebrand F, Arumugam M, Backhed F, Blaser MJ, Bushman FD, et al. Enterotypes in the landscape of gut microbial community composition. Nature Microbiol. 2018;3(1):8–16. doi: 10.1038/s41564-017-0072-8 29255284; PubMed Central PMCID: PMC5832044.
30. Segata N, Waldron L, Ballarini A, Narasimhan V, Jousson O, Huttenhower C. Metagenomic microbial community profiling using unique clade-specific marker genes. Nature Methods. 2012;9(8):811–4. doi: 10.1038/nmeth.2066 22688413; PubMed Central PMCID: PMC3443552.
31. Tett A, Huang KD, Asnicar F, Fehlner-Peach H, Pasolli E, Karcher N, et al. The Prevotella copri Complex Comprises Four Distinct Clades Underrepresented in Westernized Populations. Cell Host Microbe. 2019;26(5):666–79 e7. doi: 10.1016/j.chom.2019.08.018 31607556; PubMed Central PMCID: PMC6854460.
32. Bacic M, Parker AC, Stagg J, Whitley HP, Wells WG, Jacob LA, et al. Genetic and structural analysis of the Bacteroides conjugative transposon CTn341. J Bacteriol. 2005;187(8):2858–69. doi: 10.1128/JB.187.8.2858-2869.2005 15805532; PubMed Central PMCID: PMC1070377.
33. 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. 2016;535(7612):435–9. doi: 10.1038/nature18927 27409808; PubMed Central PMCID: PMC4983458.
34. Jiang X, Hall AB, Xavier RJ, Alm EJ. Comprehensive analysis of chromosomal mobile genetic elements in the gut microbiome reveals phylum-level niche-adaptive gene pools. PloS One. 2019;14(12):e0223680. doi: 10.1371/journal.pone.0223680 31830054;
35. Pantosti A, Tzianabos AO, Onderdonk AB, Kasper DL. Immunochemical characterization of two surface polysaccharides of Bacteroides fragilis. Infect Immun. 1991;59(6):2075–82. Epub 1991/06/01. doi: 10.1128/IAI.59.6.2075-2082.1991 2037368; PubMed Central PMCID: PMC257968.
36. Chin CS, Peluso P, Sedlazeck FJ, Nattestad M, Concepcion GT, Clum A, et al. Phased diploid genome assembly with single-molecule real-time sequencing. Nature Methods. 2016;13(12):1050–4. doi: 10.1038/nmeth.4035 27749838; PubMed Central PMCID: PMC5503144.
37. Kolmogorov M, Yuan J, Lin Y, Pevzner PA. Assembly of long, error-prone reads using repeat graphs. Nature Biotechnol. 2019;37(5):540–6. doi: 10.1038/s41587-019-0072-8 30936562.
38. Wick RR, Schultz MB, Zobel J, Holt KE. Bandage: interactive visualization of de novo genome assemblies. Bioinformatics. 2015;31(20):3350–2. doi: 10.1093/bioinformatics/btv383 26099265; PubMed Central PMCID: PMC4595904.
39. Koren S, Walenz BP, Berlin K, Miller JR, Bergman NH, Phillippy AM. Canu: scalable and accurate long-read assembly via adaptive k-mer weighting and repeat separation. Genome Res. 2017;27(5):722–36. doi: 10.1101/gr.215087.116 28298431; PubMed Central PMCID: PMC5411767.
40. Kolmogorov M, Armstrong J, Raney BJ, Streeter I, Dunn M, Yang F, et al. Chromosome assembly of large and complex genomes using multiple references. Genome Res. 2018;28(11):1720–32. doi: 10.1101/gr.236273.118 30341161; PubMed Central PMCID: PMC6211643.
41. Hyatt D, Chen GL, Locascio PF, Land ML, Larimer FW, Hauser LJ. Prodigal: prokaryotic gene recognition and translation initiation site identification. BMC Bioinformatics. 2010;11. doi: 10.1186/1471-2105-11-119 20211023
42. Seemann T. Prokka: rapid prokaryotic genome annotation. Bioinformatics. 2014;30(14):2068–9. doi: 10.1093/bioinformatics/btu153 24642063.
43. Krawczyk PS, Lipinski L, Dziembowski A. PlasFlow: predicting plasmid sequences in metagenomic data using genome signatures. Nucleic Acids Res. 2018;46(6):e35. doi: 10.1093/nar/gkx1321 29346586; PubMed Central PMCID: PMC5887522.
44. Sievers F, Wilm A, Dineen D, Gibson TJ, Karplus K, Li W. Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Molecular systems biology. 2011;7. doi: 10.1038/msb.2011.75 21988835
45. Kumar S, Stecher G, Li M, Knyaz C, Tamura K. MEGA X: Molecular Evolutionary Genetics Analysis across Computing Platforms. Mol. Biol. Evolution 2018;35(6):1547–9. doi: 10.1093/molbev/msy096 29722887.
46. Stamatakis A. RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies. Bioinformatics. 2014;30(9):1312–3. doi: 10.1093/bioinformatics/btu033 24451623; PubMed Central PMCID: PMC3998144.
47. Fu L, Niu B, Zhu Z, Wu S, Li W. CD-HIT: accelerated for clustering the next-generation sequencing data. Bioinformatics. 2012;28(23):3150–2. doi: 10.1093/bioinformatics/bts565 23060610; PubMed Central PMCID: PMC3516142.
48. Liu W, Zhang J, Wu C, Cai S, Huang W, Chen J, et al. Unique Features of Ethnic Mongolian Gut Microbiome revealed by metagenomic analysis. Sci Rep 2016;6:34826. doi: 10.1038/srep34826 27708392; PubMed Central PMCID: PMC5052615.
49. Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464(7285):59–65. doi: 10.1038/nature08821 20203603; PubMed Central PMCID: PMC3779803.
50. Rampelli S, Schnorr SL, Consolandi C, Turroni S, Severgnini M, Peano C, et al. Metagenome Sequencing of the Hadza Hunter-Gatherer Gut Microbiota. Curr Biol. 2015;25(13):1682–93. doi: 10.1016/j.cub.2015.04.055 25981789.
51. D’Amico F, Soverini M, Zama D, Consolandi C, Severgnini M, Prete A, et al. Gut resistome plasticity in pediatric patients undergoing hematopoietic stem cell transplantation. Sci Rep. 2019;9(1):5649. doi: 10.1038/s41598-019-42222-w 30948795; PubMed Central PMCID: PMC6449395.
52. Yachida S, Mizutani S, Shiroma H, Shiba S, Nakajima T, Sakamoto T, et al. Metagenomic and metabolomic analyses reveal distinct stage-specific phenotypes of the gut microbiota in colorectal cancer. Nat Med. 2019;25(6):968–76. doi: 10.1038/s41591-019-0458-7 31171880.
53. Pasolli E, Asnicar F, Manara S, Zolfo M, Karcher N, Armanini F, et al. Extensive Unexplored Human Microbiome Diversity Revealed by Over 150,000 Genomes from Metagenomes Spanning Age, Geography, and Lifestyle. Cell. 2019;176(3):649–62 e20. doi: 10.1016/j.cell.2019.01.001 30661755; PubMed Central PMCID: PMC6349461.
54. Obregon-Tito AJ, Tito RY, Metcalf J, Sankaranarayanan K, Clemente JC, Ursell LK, et al. Subsistence strategies in traditional societies distinguish gut microbiomes. Nature communications. 2015;6:6505. doi: 10.1038/ncomms7505 25807110; PubMed Central PMCID: PMC4386023.
55. Karlsson FH, Tremaroli V, Nookaew I, Bergstrom G, Behre CJ, Fagerberg B, et al. Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature. 2013;498(7452):99–103. doi: 10.1038/nature12198 23719380.
56. Vangay P, Johnson AJ, Ward TL, Al-Ghalith GA, Shields-Cutler RR, Hillmann BM, et al. US Immigration Westernizes the Human Gut Microbiome. Cell. 2018;175(4):962–72 e10. doi: 10.1016/j.cell.2018.10.029 30388453; PubMed Central PMCID: PMC6498444.
57. Lloyd-Price J, Arze C, Ananthakrishnan AN, Schirmer M, Avila-Pacheco J, Poon TW, et al. Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases. Nature. 2019;569(7758):655–62. doi: 10.1038/s41586-019-1237-9 31142855; PubMed Central PMCID: PMC6650278.
58. Flannery JE, Stagaman K, Burns AR, Hickey RJ, Roos LE, Giuliano RJ, et al. Gut feelings begin in childhood: how the gut metagenome links to early environment, caregiving, and behavior. bioRxiv 2019. doi: 10.1101/568717
Článek vyšel v časopise
PLOS Genetics
2021 Číslo 4
- S diagnostikou Parkinsonovy nemoci může nově pomoci AI nástroj pro hodnocení mrkacího reflexu
- Proč při poslechu některé muziky prostě musíme tančit?
- Chůze do schodů pomáhá prodloužit život a vyhnout se srdečním chorobám
- Metamizol jako analgetikum první volby: kdy, pro koho, jak a proč?
- „Jednohubky“ z klinického výzkumu – 2024/44
Nejčtenější v tomto čísle
- Aicardi-Goutières syndrome-associated gene SAMHD1 preserves genome integrity by preventing R-loop formation at transcription–replication conflict regions
- Functional assessment of the “two-hit” model for neurodevelopmental defects in Drosophila and X. laevis
- Pathways and signatures of mutagenesis at targeted DNA nicks
- Using genetic variants to evaluate the causal effect of cholesterol lowering on head and neck cancer risk: A Mendelian randomization study
