1887

Abstract

Bacterial genome sequences consistently contain many more biosynthetic gene clusters encoding specialized metabolites than predicted by the compounds discovered from the respective strains. One hypothesis invoked to explain the cryptic nature of these gene clusters is that standard laboratory conditions do not provide the environmental cues needed to trigger gene expression. A potential source of such cues is other members of the bacterial community, which are logical targets for competitive interactions. In this study, we examined the effects of such interactions on specialized metabolism in the marine actinomycete Salinispora tropica. The results show that antibiotic activities and the concentration of some small molecules increase in the presence of co-occurring bacterial strains relative to monocultures. Some increases in antibiotic activity could be linked to nutrient depletion by the competitor as opposed to the production of a chemical cue. Other increases were correlated with the production of specific compounds by S. tropica. In particular, one interaction with a Vibrio sp. consistently induced antibiotic activity and was associated with parent ions that were unique to this interaction, although the associated compound could not be identified. This study provides insight into the metabolomic complexities of bacterial interactions and baseline information for future genome mining efforts.

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2018-06-07
2019-10-14
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References

  1. Newman DJ, Cragg GM. Natural products as sources of new drugs over the last 25 years. J Nat Prod 2007;70:461–477 [CrossRef][PubMed]
    [Google Scholar]
  2. Bérdy J. Bioactive microbial metabolites. J Antibiot 2005;58:1–26 [CrossRef][PubMed]
    [Google Scholar]
  3. Wietz M, Duncan K, Patin NV, Jensen PR. Antagonistic interactions mediated by marine bacteria: the role of small molecules. J Chem Ecol 2013;39:879–891 [CrossRef][PubMed]
    [Google Scholar]
  4. Andersson DI, Hughes D. Microbiological effects of sublethal levels of antibiotics. Nat Rev Microbiol 2014;12:465–478 [CrossRef][PubMed]
    [Google Scholar]
  5. Nett M, Ikeda H, Moore BS. Genomic basis for natural product biosynthetic diversity in the actinomycetes. Nat Prod Rep 2009;26:1362–1384 [CrossRef][PubMed]
    [Google Scholar]
  6. Letzel AC, Li J, Amos GCA, Millán-Aguiñaga N, Ginigini J et al. Genomic insights into specialized metabolism in the marine actinomycete Salinispora. Environ Microbiol 2017;19:3660–3673 [CrossRef][PubMed]
    [Google Scholar]
  7. Hibbing ME, Fuqua C, Parsek MR, Peterson SB. Bacterial competition: surviving and thriving in the microbial jungle. Nat Rev Microbiol 2010;8:15–25 [CrossRef][PubMed]
    [Google Scholar]
  8. Abrudan MI, Smakman F, Grimbergen AJ, Westhoff S, Miller EL et al. Socially mediated induction and suppression of antibiosis during bacterial coexistence. Proc Natl Acad Sci USA 2015;112:11054–11059 [CrossRef][PubMed]
    [Google Scholar]
  9. Kinkel LL, Schlatter DC, Xiao K, Baines AD. Sympatric inhibition and niche differentiation suggest alternative coevolutionary trajectories among Streptomycetes. Isme J 2014;8:249–256 [CrossRef][PubMed]
    [Google Scholar]
  10. Rigali S, Titgemeyer F, Barends S, Mulder S, Thomae AW et al. Feast or famine: the global regulator DasR links nutrient stress to antibiotic production by Streptomyces. EMBO Rep 2008;9:670–675 [CrossRef][PubMed]
    [Google Scholar]
  11. van Wezel GP, McDowall KJ. The regulation of the secondary metabolism of Streptomyces: new links and experimental advances. Nat Prod Rep 2011;28:1311 [CrossRef][PubMed]
    [Google Scholar]
  12. Pettit RK. Mixed fermentation for natural product drug discovery. Appl Microbiol Biotechnol 2009;83:19–25 [CrossRef][PubMed]
    [Google Scholar]
  13. Bertrand S, Schumpp O, Bohni N, Monod M, Gindro K et al. De novo production of metabolites by fungal co-culture of Trichophyton rubrum and Bionectria ochroleuca. J Nat Prod 2013;76:1157–1165 [CrossRef][PubMed]
    [Google Scholar]
  14. Oh DC, Kauffman CA, Jensen PR, Fenical W. Induced production of emericellamides A and B from the marine-derived fungus Emericella sp. in competing co-culture. J Nat Prod 2007;70:515–520 [CrossRef][PubMed]
    [Google Scholar]
  15. Cueto M, Jensen PR, Kauffman C, Fenical W, Lobkovsky E et al. Pestalone, a new antibiotic produced by a marine fungus in response to bacterial challenge. J Nat Prod 2001;64:1444–1446 [CrossRef][PubMed]
    [Google Scholar]
  16. Briand E, Bormans M, Gugger M, Dorrestein PC, Gerwick WH. Changes in secondary metabolic profiles of Microcystis aeruginosa strains in response to intraspecific interactions. Environ Microbiol 2016;18:384–400 [CrossRef][PubMed]
    [Google Scholar]
  17. Paul C, Mausz MA, Pohnert G. A co-culturing/metabolomics approach to investigate chemically mediated interactions of planktonic organisms reveals influence of bacteria on diatom metabolism. Metabolomics 2013;9:349–359 [CrossRef]
    [Google Scholar]
  18. Seyedsayamdost MR, Case RJ, Kolter R, Clardy J. The Jekyll-and-Hyde chemistry of Phaeobacter gallaeciensis. Nat Chem 2011;3:331–335 [CrossRef][PubMed]
    [Google Scholar]
  19. Slattery M, Rajbhandari I, Wesson K. Competition-mediated antibiotic induction in the marine bacterium Streptomyces tenjimariensis. Microb Ecol 2001;41:90–96 [CrossRef][PubMed]
    [Google Scholar]
  20. Onaka H, Mori Y, Igarashi Y, Furumai T. Mycolic acid-containing bacteria induce natural-product biosynthesis in Streptomyces species. Appl Environ Microbiol 2011;77:400–406 [CrossRef][PubMed]
    [Google Scholar]
  21. Dashti Y, Grkovic T, Abdelmohsen UR, Hentschel U, Quinn RJ. Production of induced secondary metabolites by a co-culture of sponge-associated actinomycetes, Actinokineospora sp. EG49 and Nocardiopsis sp. RV163. Mar Drugs 2014;12:3046–3059 [CrossRef][PubMed]
    [Google Scholar]
  22. Trischman JA, Oeffner RE, de Luna MG, Kazaoka M. Competitive induction and enhancement of indole and a diketopiperazine in marine bacteria. Mar Biotechnol 2004;6:215–220 [CrossRef][PubMed]
    [Google Scholar]
  23. Schroeckh V, Scherlach K, Nützmann HW, Shelest E, Schmidt-Heck W et al. Intimate bacterial-fungal interaction triggers biosynthesis of archetypal polyketides in Aspergillus nidulans. Proc Natl Acad Sci USA 2009;106:14558–14563 [CrossRef][PubMed]
    [Google Scholar]
  24. McKenzie NL, Thaker M, Koteva K, Hughes DW, Wright GD et al. Induction of antimicrobial activities in heterologous streptomycetes using alleles of the Streptomyces coelicolor gene absA1. J Antibiot 2010;63:177–182 [CrossRef][PubMed]
    [Google Scholar]
  25. Yoon V, Nodwell JR. Activating secondary metabolism with stress and chemicals. J Ind Microbiol Biotechnol 2014;41:415–424 [CrossRef][PubMed]
    [Google Scholar]
  26. Aravindraja C, Viszwapriya D, Karutha Pandian S. Ultradeep 16S rRNA sequencing analysis of geographically similar but diverse unexplored marine samples reveal varied bacterial community composition. PLoS One 2013;8:e76724 [CrossRef][PubMed]
    [Google Scholar]
  27. Gaidos E, Rusch A, Ilardo M. Ribosomal tag pyrosequencing of DNA and RNA from benthic coral reef microbiota: community spatial structure, rare members and nitrogen-cycling guilds. Environ Microbiol 2011;13:1138–1152 [CrossRef][PubMed]
    [Google Scholar]
  28. Gobet A, Böer SI, Huse SM, van Beusekom JE, Quince C et al. Diversity and dynamics of rare and of resident bacterial populations in coastal sands. Isme J 2012;6:542–553 [CrossRef][PubMed]
    [Google Scholar]
  29. Musat N, Werner U, Knittel K, Kolb S, Dodenhof T et al. Microbial community structure of sandy intertidal sediments in the North Sea, Sylt-Rømø Basin, Wadden Sea. Syst Appl Microbiol 2006;29:333–348 [CrossRef][PubMed]
    [Google Scholar]
  30. Patin NV, Schorn M, Aguinaldo K, Lincecum T, Moore BS et al. Effects of actinomycete secondary metabolites on sediment microbial communities. Appl Environ Microbiol 2017;83:e02676-16 [CrossRef][PubMed]
    [Google Scholar]
  31. Wang Y, Sheng HF, He Y, Wu JY, Jiang YX et al. Comparison of the levels of bacterial diversity in freshwater, intertidal wetland, and marine sediments by using millions of illumina tags. Appl Environ Microbiol 2012;78:8264–8271 [CrossRef][PubMed]
    [Google Scholar]
  32. Zinger L, Amaral-Zettler LA, Fuhrman JA, Horner-Devine MC, Huse SM et al. Global patterns of bacterial beta-diversity in seafloor and seawater ecosystems. PLoS One 2011;6:e24570 [CrossRef][PubMed]
    [Google Scholar]
  33. Shade A, Jones SE, Caporaso JG, Handelsman J, Knight R et al. Conditionally rare taxa disproportionately contribute to temporal changes in microbial diversity. MBio 2014;5:e01371-14 [CrossRef][PubMed]
    [Google Scholar]
  34. Ramirez KS, Knight CG, de Hollander M, Brearley FQ, Constantinides B et al. Detecting macroecological patterns in bacterial communities across independent studies of global soils. Nat Microbiol 2018;3:189–196 [CrossRef][PubMed]
    [Google Scholar]
  35. Lynch MD, Neufeld JD. Ecology and exploration of the rare biosphere. Nat Rev Microbiol 2015;13:217–229 [CrossRef][PubMed]
    [Google Scholar]
  36. Patin NV, Duncan KR, Dorrestein PC, Jensen PR. Competitive strategies differentiate closely related species of marine actinobacteria. Isme J 2016;10:478–490 [CrossRef][PubMed]
    [Google Scholar]
  37. Burgess JG, Jordan EM, Bregu M, Mearns-Spragg A, Boyd KG. Microbial antagonism: a neglected avenue of natural products research. J Biotechnol 1999;70:27–32 [CrossRef][PubMed]
    [Google Scholar]
  38. Watrous J, Roach P, Alexandrov T, Heath BS, Yang JY et al. Mass spectral molecular networking of living microbial colonies. Proc Natl Acad Sci USA 2012;109:E1743E1752 [CrossRef][PubMed]
    [Google Scholar]
  39. Wang M, Carver JJ, Phelan VV, Sanchez LM, Garg N et al. Sharing and community curation of mass spectrometry data with global natural products social molecular networking. Nat Biotechnol 2016;34:828–837 [CrossRef][PubMed]
    [Google Scholar]
  40. Cline MS, Smoot M, Cerami E, Kuchinsky A, Landys N et al. Integration of biological networks and gene expression data using Cytoscape. Nat Protoc 2007;2:2366–2382 [CrossRef][PubMed]
    [Google Scholar]
  41. Jensen PR, Moore BS, Fenical W. The marine actinomycete genus Salinispora: a model organism for secondary metabolite discovery. Nat Prod Rep 2015;32:738–751 [CrossRef][PubMed]
    [Google Scholar]
  42. Kersten RD, Lane AL, Nett M, Richter TK, Duggan BM et al. Bioactivity-guided genome mining reveals the lomaiviticin biosynthetic gene cluster in Salinispora tropica. Chembiochem 2013;14:955–962 [CrossRef][PubMed]
    [Google Scholar]
  43. Richter TK, Hughes CC, Moore BS. Sioxanthin, a novel glycosylated carotenoid, reveals an unusual subclustered biosynthetic pathway. Environ Microbiol 2015;17:2158–2171 [CrossRef][PubMed]
    [Google Scholar]
  44. Yang JY, Sanchez LM, Rath CM, Liu X, Boudreau PD et al. Molecular networking as a dereplication strategy. J Nat Prod 2013;76:1686–1699 [CrossRef][PubMed]
    [Google Scholar]
  45. Miyanaga A, Janso JE, McDonald L, He M, Liu H et al. Discovery and assembly-line biosynthesis of the lymphostin pyrroloquinoline alkaloid family of mTOR inhibitors in Salinispora bacteria. J Am Chem Soc 2011;133:13311–13313 [CrossRef][PubMed]
    [Google Scholar]
  46. Scherlach K, Hertweck C. Triggering cryptic natural product biosynthesis in microorganisms. Org Biomol Chem 2009;7:1753–1760 [CrossRef][PubMed]
    [Google Scholar]
  47. Bertrand S, Bohni N, Schnee S, Schumpp O, Gindro K et al. Metabolite induction via microorganism co-culture: a potential way to enhance chemical diversity for drug discovery. Biotechnol Adv 2014;32:1180–1204 [CrossRef][PubMed]
    [Google Scholar]
  48. Rutledge PJ, Challis GL. Discovery of microbial natural products by activation of silent biosynthetic gene clusters. Nat Rev Microbiol 2015;13:509–523 [CrossRef][PubMed]
    [Google Scholar]
  49. Paz-Yepes J, Brahamsha B, Palenik B. Role of a microcin-C-like biosynthetic gene cluster in allelopathic interactions in marine Synechococcus. Proc Natl Acad Sci USA 2013;110:12030–12035 [CrossRef][PubMed]
    [Google Scholar]
  50. Jensen PR, Williams PG, Oh DC, Zeigler L, Fenical W. Species-specific secondary metabolite production in marine actinomycetes of the genus Salinispora. Appl Environ Microbiol 2007;73:1146–1152 [CrossRef][PubMed]
    [Google Scholar]
  51. Zhu H, Sandiford SK, van Wezel GP. Triggers and cues that activate antibiotic production by actinomycetes. J Ind Microbiol Biotechnol 2014;41:371–386 [CrossRef][PubMed]
    [Google Scholar]
  52. Baron SS, Rowe JJ. Antibiotic action of pyocyanin. Antimicrob Agents Chemother 1981;20:814–820 [CrossRef][PubMed]
    [Google Scholar]
  53. Liu GY, Nizet V. Color me bad: microbial pigments as virulence factors. Trends Microbiol 2009;17:406–413 [CrossRef][PubMed]
    [Google Scholar]
  54. Liu GY, Essex A, Buchanan JT, Datta V, Hoffman HM et al. Staphylococcus aureus golden pigment impairs neutrophil killing and promotes virulence through its antioxidant activity. J Exp Med 2005;202:209–215 [CrossRef][PubMed]
    [Google Scholar]
  55. Yang YL, Xu Y, Kersten RD, Liu WT, Meehan MJ et al. Connecting chemotypes and phenotypes of cultured marine microbial assemblages by imaging mass spectrometry. Angew Chem Int Ed Engl 2011;50:5839–5842 [CrossRef][PubMed]
    [Google Scholar]
  56. Traxler MF, Watrous JD, Alexandrov T, Dorrestein PC, Kolter R. Interspecies interactions stimulate diversification of the Streptomyces coelicolor secreted metabolome. MBio 2013;4:e00459-13 [CrossRef][PubMed]
    [Google Scholar]
  57. Roberts AA, Schultz AW, Kersten RD, Dorrestein PC, Moore BS. Iron acquisition in the marine actinomycete genus Salinispora is controlled by the desferrioxamine family of siderophores. FEMS Microbiol Lett 2012;335:95–103 [CrossRef][PubMed]
    [Google Scholar]
  58. Eloe-Fadrosh EA, Ivanova NN, Woyke T, Kyrpides NC. Metagenomics uncovers gaps in amplicon-based detection of microbial diversity. Nat Microbiol 2016;1:15032 [CrossRef][PubMed]
    [Google Scholar]
  59. Ziemert N, Lechner A, Wietz M, Millán-Aguiñaga N, Chavarria KL et al. Diversity and evolution of secondary metabolism in the marine actinomycete genus Salinispora. Proc Natl Acad Sci USA 2014;111:E1130E1139 [CrossRef][PubMed]
    [Google Scholar]
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