1887

Microbial Genomics logo

Volume 10, Issue 1

Prophages: an integral but understudied component of the human microbiome Open Access

Abstract

Phages integrated into a bacterial genome – called prophages – continuously monitor the vigour of the host bacteria to determine when to escape the genome and to protect their host from other phage infections, and they may provide genes that promote bacterial growth. Prophages are essential to almost all microbiomes, including the human microbiome. However, most human microbiome studies have focused on bacteria, ignoring free and integrated phages, so we know little about how these prophages affect the human microbiome. To address this gap in our knowledge, we compared the prophages identified in 14 987 bacterial genomes isolated from human body sites to characterize prophage DNA in the human microbiome. Here, we show that prophage DNA is ubiquitous, comprising on average 1–5 % of each bacterial genome. The prophage content per genome varies with the isolation site on the human body, the health of the human and whether the disease was symptomatic. The presence of prophages promotes bacterial growth and sculpts the microbiome. However, the disparities caused by prophages vary throughout the body.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): disease , human microbiome , phage and prophage
Funding
This study was supported by the:
  • National Institute of Diabetes and Digestive and Kidney Diseases (Award RC2DK116713)
    • Principle Award Recipient: RobertA Edwards
  • Australian Research Council (Award DP220102915)
    • Principle Award Recipient: RobertA Edwards
© 2024 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
Loading

Article metrics loading...

/content/journal/mgen/10.1099/mgen.0.001166
2024-01-24
2024-04-28
Loading full text...

Full text loading...

/deliver/fulltext/mgen/10/1/mgen001166.html?itemId=/content/journal/mgen/10.1099/mgen.0.001166&mimeType=html&fmt=ahah

References

  1. McKerral JC, Papudeshi B, Inglis LK, Roach MJ, Decewicz P et al. The promise and pitfalls of prophages. bioRxiv 20232023.04.20.537752 [View Article] [PubMed]
     [Google Scholar]
  2. Falony G, Joossens M, Vieira-Silva S, Wang J, Darzi Y et al. Population-level analysis of gut microbiome variation. Science 2016; 352:560–564 [View Article] [PubMed]
     [Google Scholar]
  3. Knowles B, Silveira CB, Bailey BA, Barott K, Cantu VA et al. Lytic to temperate switching of viral communities. Nature 2016; 539:466–470 [View Article] [PubMed]
     [Google Scholar]
  4. Wattam AR, Davis JJ, Assaf R, Boisvert S, Brettin T et al. Improvements to PATRIC, the all-bacterial bioinformatics database and analysis resource center. Nucleic Acids Res 2017; 45:D535–D542 [View Article] [PubMed]
     [Google Scholar]
  5. Mirsepasi-Lauridsen HC, Vrankx K, Engberg J, Friis-Møller A, Brynskov J et al. Disease-specific enteric microbiome dysbiosis in inflammatory bowel disease. Front Med 2018; 5:304 [View Article]
     [Google Scholar]
  6. Inglis LK, Edwards RA. How metagenomics has transformed our understanding of bacteriophages in microbiome research. Microorganisms 2022; 10:1671 [View Article] [PubMed]
     [Google Scholar]
  7. Brüssow H. The human microbiome project at ten years - some critical comments and reflections on “our third genome”, the human virome. Microbiome Res Rep 2023; 2:7 [View Article] [PubMed]
     [Google Scholar]
  8. Riedl RA, Burnett CML, Pearson NA, Reho JJ, Mokadem M et al. Gut microbiota represent a major thermogenic biomass. Function 2021; 2:zqab019 [View Article] [PubMed]
     [Google Scholar]
  9. Sender R, Fuchs S, Milo R. Revised estimates for the number of human and bacteria cells in the body. PLoS Biol 2016; 14:e1002533 [View Article] [PubMed]
     [Google Scholar]
  10. Shkoporov AN, Hill C. Bacteriophages of the human gut: The “Known Unknown” of the microbiome. Cell Host & Microbe 2019; 25:195–209 [View Article]
     [Google Scholar]
  11. Yagi K, Huffnagle GB, Lukacs NW, Asai N. The lung microbiome during health and disease. IJMS 2021; 22:10872 [View Article]
     [Google Scholar]
  12. Knowles B, Bailey B, Boling L, Breitbart M, Cobián-Güemes A et al. Variability and host density independence in inductions-based estimates of environmental lysogeny. Nat Microbiol 2017; 2:17064 [View Article] [PubMed]
     [Google Scholar]
  13. Suttle CA. Marine viruses--major players in the global ecosystem. Nat Rev Microbiol 2007; 5:801–812 [View Article] [PubMed]
     [Google Scholar]
  14. Dutilh BE, Cassman N, McNair K, Sanchez SE, Silva GGZ et al. A highly abundant bacteriophage discovered in the unknown sequences of human faecal metagenomes. Nat Commun 2014; 5:1–11 [View Article]
     [Google Scholar]
  15. Camarillo-Guerrero LF, Almeida A, Rangel-Pineros G, Finn RD, Lawley TD. Massive expansion of human gut bacteriophage diversity. Cell 2021; 184:1098–1109 [View Article] [PubMed]
     [Google Scholar]
  16. Lwoff A. Lysogeny. Bacteriol Rev 1953; 17:269–337 [View Article] [PubMed]
     [Google Scholar]
  17. Zinder ND. Lysogenization and superinfection immunity in Salmonella. Virology 1958; 5:291–326 [View Article] [PubMed]
     [Google Scholar]
  18. Mavrich TN, Hatfull GF. Evolution of superinfection immunity in cluster A mycobacteriophages. mBio 2019; 10:e00971-19 [View Article] [PubMed]
     [Google Scholar]
  19. Castillo D, Kauffman K, Hussain F, Kalatzis P, Rørbo N et al. Widespread distribution of prophage-encoded virulence factors in marine Vibrio communities. Sci Rep 2018; 8:9973 [View Article] [PubMed]
     [Google Scholar]
  20. Sweere JM, Van Belleghem JD, Ishak H, Bach MS, Popescu M et al. Bacteriophage trigger antiviral immunity and prevent clearance of bacterial infection. Science 2019; 363:eaat9691 [View Article] [PubMed]
     [Google Scholar]
  21. Bielaszewska M, Idelevich EA, Zhang W, Bauwens A, Schaumburg F et al. Effects of antibiotics on Shiga toxin 2 production and bacteriophage induction by epidemic Escherichia coli O104:H4 strain. Antimicrob Agents Chemother 2012; 56:3277–3282 [View Article] [PubMed]
     [Google Scholar]
  22. von Wintersdorff CJH, Penders J, van Niekerk JM, Mills ND, Majumder S et al. Dissemination of antimicrobial resistance in microbial ecosystems through horizontal gene transfer. Front Microbiol 2016; 7:173 [View Article]
     [Google Scholar]
  23. Waldor MK, Mekalanos JJ. Lysogenic conversion by a filamentous phage encoding cholera toxin. Science 1996; 272:1910–1914 [View Article] [PubMed]
     [Google Scholar]
  24. Ptashne M. A Genetic Switch: Phage Lambda Revisited Cold Spring Harbor, N.Y: CSHL press; 2004
     [Google Scholar]
  25. Erez Z, Steinberger-Levy I, Shamir M, Doron S, Stokar-Avihail A et al. Communication between viruses guides lysis-lysogeny decisions. Nature 2017; 541:488–493 [View Article] [PubMed]
     [Google Scholar]
  26. Silveira CB, Luque A, Rohwer F. The landscape of lysogeny across microbial community density, diversity and energetics. Environ Microbiol 2021; 23:4098–4111 [View Article] [PubMed]
     [Google Scholar]
  27. Flinders University Deep Thought (HPC) Flinders University; 2021
     [Google Scholar]
  28. Akhter S, Aziz RK, Edwards RA. PhiSpy: a novel algorithm for finding prophages in bacterial genomes that combines similarity- and composition-based strategies. Nucleic Acids Res 2012; 40:e126 [View Article] [PubMed]
     [Google Scholar]
  29. McNair K, Zhou C, Dinsdale EA, Souza B, Edwards RA. PHANOTATE: a novel approach to gene identification in phage genomes. Bioinformatics 2019; 35:4537–4542 [View Article] [PubMed]
     [Google Scholar]
  30. Roach MJ, McNair K, Giles SK, Inglis LK, Pargin E et al. Philympics 2021: prophage predictions perplex programs. F1000Res 2021; 10:758 [View Article]
     [Google Scholar]
  31. Inglis L, Edwards R. Prophages in Humans Flinders University; 2023
     [Google Scholar]
  32. Wattam AR, Abraham D, Dalay O, Disz TL, Driscoll T et al. PATRIC, the bacterial bioinformatics database and analysis resource. Nucleic Acids Res 2014; 42:D581–91 [View Article] [PubMed]
     [Google Scholar]
  33. Chen C, Song X, Wei W, Zhong H, Dai J et al. The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases. Nat Commun 2017; 8:875 [View Article]
     [Google Scholar]
  34. Nardone G, Compare D. The human gastric microbiota: Is it time to rethink the pathogenesis of stomach diseases?. United European Gastroenterol J 2015; 3:255–260 [View Article] [PubMed]
     [Google Scholar]
  35. Kumpitsch C, Koskinen K, Schöpf V, Moissl-Eichinger C. The microbiome of the upper respiratory tract in health and disease. BMC Biol 2019; 17:87 [View Article] [PubMed]
     [Google Scholar]
  36. O’Dwyer DN, Dickson RP, Moore BB. The lung microbiome, immunity, and the pathogenesis of chronic lung disease. J Immunol 2016; 196:4839–4847 [View Article] [PubMed]
     [Google Scholar]
  37. Breitbart M, Rohwer F. Method for discovering novel DNA viruses in blood using viral particle selection and shotgun sequencing. Biotechniques 2005; 39:729–736 [View Article] [PubMed]
     [Google Scholar]
  38. Païssé S, Valle C, Servant F, Courtney M, Burcelin R et al. Comprehensive description of blood microbiome from healthy donors assessed by 16S targeted metagenomic sequencing. Transfusion 2016; 56:1138–1147 [View Article] [PubMed]
     [Google Scholar]
  39. Martín V, Maldonado-Barragán A, Moles L, Rodriguez-Baños M, Campo RD et al. Sharing of bacterial strains between breast milk and infant feces. J Hum Lact 2012; 28:36–44 [View Article] [PubMed]
     [Google Scholar]
  40. Kogan MI, Naboka YL, Ibishev KS, Gudima IA, Naber KG. Human urine is not sterile - shift of paradigm. Urol Int 2015; 94:445–452 [View Article] [PubMed]
     [Google Scholar]
  41. Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A et al. A core gut microbiome in obese and lean twins. Nature 2009; 457:480–484 [View Article] [PubMed]
     [Google Scholar]
  42. Lloyd-Price J, Abu-Ali G, Huttenhower C. The healthy human microbiome. Genome Med 2016; 8:51 [View Article] [PubMed]
     [Google Scholar]
  43. Rodriguez-Brito B, Li L, Wegley L, Furlan M, Angly F et al. Viral and microbial community dynamics in four aquatic environments. ISME J 2010; 4:739–751 [View Article] [PubMed]
     [Google Scholar]
  44. Shkoporov AN, Clooney AG, Sutton TDS, Ryan FJ, Daly KM et al. The human gut virome is highly diverse, stable, and individual specific. Cell Host Microbe 2019; 26:527–541 [View Article] [PubMed]
     [Google Scholar]
  45. de la Calle F. Marine microbiome as source of natural products. Microb Biotechnol 2017; 10:1293–1296 [View Article] [PubMed]
     [Google Scholar]
  46. Lassalle F, Spagnoletti M, Fumagalli M, Shaw L, Dyble M et al. Oral microbiomes from hunter-gatherers and traditional farmers reveal shifts in commensal balance and pathogen load linked to diet. Mol Ecol 2018; 27:182–195 [View Article] [PubMed]
     [Google Scholar]
  47. Suzuki TA, Worobey M. Geographical variation of human gut microbial composition. Biol Lett 2014; 10:20131037 [View Article] [PubMed]
     [Google Scholar]
  48. Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG et al. Human gut microbiome viewed across age and geography. Nature 2012; 486:222–227 [View Article] [PubMed]
     [Google Scholar]
  49. Gaulke CA, Sharpton TJ. The influence of ethnicity and geography on human gut microbiome composition. Nat Med 2018; 24:1495–1496 [View Article] [PubMed]
     [Google Scholar]
  50. Paterson JS, Smith RJ, McKerral JC, Dann LM, Launer E et al. A hydrocarbon-contaminated aquifer reveals a Piggyback-the-persistent viral strategy. FEMS Microbiol Ecol 2019; 95:95 [View Article] [PubMed]
     [Google Scholar]
  51. de Steenhuijsen Piters WAA, Huijskens EGW, Wyllie AL, Biesbroek G, van den Bergh MR et al. Dysbiosis of upper respiratory tract microbiota in elderly pneumonia patients. ISME J 2016; 10:97–108 [View Article] [PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/mgen/10.1099/mgen.0.001166
Loading
Prophages: an integral but understudied component of the human microbiome
M Gen 10, 001166 (2024); https://doi.org/10.1099/mgen.0.001166
/content/journal/mgen/10.1099/mgen.0.001166
/content/journal/mgen/10.1099/mgen.0.001166
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error