Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Special Feature: Review Article
  • Published:

Role of symbiosis in the discovery of novel antibiotics

The Journal of Antibiotics volume 73, pages 490–503 (2020)Cite this article

Subjects

Abstract

Antibiotic resistance has been an ongoing challenge that has emerged almost immediately after the initial discovery of antibiotics and requires the development of innovative new antibiotics and antibiotic combinations that can effectively mitigate the development of resistance. More than 35,000 people die each year from antibiotic resistant infections in just the United States. This signifies the importance of identifying other alternatives to antibiotics for which resistance has developed. Virtually, all currently used antibiotics can trace their genesis to soil derived bacteria and fungi. The bacteria and fungi involved in symbiosis is an area that still remains widely unexplored for the discovery and development of new antibiotics. This brief review focuses on the challenges and opportunities in the application of symbiotic microbes and also provides an interesting platform that links natural product chemistry with evolutionary biology and ecology.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Gross M. The race against antibiotics resistance. Curr Biol. 2019;23:R859–61.

    Google Scholar 

  2. Centers for Disease Control and Prevention. Antibiotic/antimicrobial resistance (AR/AMR). 2020. https://www.cdc.gov/drugresistance/about.html.

  3. Engl T, Kroiss J, Kai M, Nechitaylo TY, Svatoš A, Kaltenpoth M. Evolutionary stability of antibiotic protection in a defensive symbiosis. Proc Natl Acad Sci USA. 2018;115:E2020–9.

    CAS  PubMed  Google Scholar 

  4. Centers for Disease Control and Prevention. Antibiotic resistance threats in the United States, 2019. 2019. https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf.

  5. Staley JT, Castenholz RW, Colwell RR, Holt JG, Kane MD, Pace NR, et al. The microbial world: foundation of the biosphere. Washington, D.C.: American Academy of Microbiology; 1997.

  6. Oulhen N, Schulz BJ, Carrier TJ. English translation of Heinrich Anton de Bary’s 1878 speech,‘Die Erscheinung der Symbiose’(‘De la symbiose’). Symbiosis. 2016;69:131–9.

    Google Scholar 

  7. Egerton FN. History of ecological sciences, Part 52: symbiosis studies. Bull Ecol Soc Am. 2015;96:80–139.

    Google Scholar 

  8. Blockley A, Elliott DR, Roberts AP, Sweet M. Symbiotic microbes from marine invertebrates: driving a new era of natural product drug discovery. Diversity. 2017;9:49.

    Google Scholar 

  9. Adnani N, Rajski SR, Bugni TS. Symbiosis-inspired approaches to antibiotic discovery. Nat Prod Rep. 2017;34:784–814.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Zhang X, Wei W, Tan R. Symbionts, a promising source of bioactive natural products. Sci China: Chem. 2015;58:1097–109.

    CAS  Google Scholar 

  11. Henkel T, Brunne RM, Müller H, Reichel F. Statistical investigation into the structural complementarity of natural products and synthetic compounds. Angew Chem, Int Ed. 1999;38:643–7.

    CAS  Google Scholar 

  12. Montaser R, Luesch H. Marine natural products: a new wave of drugs? Future Med Chem. 2011;3:1475–89.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Wang G. Diversity and biotechnological potential of the sponge-associated microbial consortia. J Ind Microbiol Biotechnol. 2006;33:545.

    CAS  PubMed  Google Scholar 

  14. Reveillaud J, Maignien L, Eren AM, Huber JA, Apprill A, Sogin ML, et al. Host-specificity among abundant and rare taxa in the sponge microbiome. ISME J. 2014;8:1198–209.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Schmitt S, Tsai P, Bell J, Fromont J, Ilan M, Lindquist N, et al. Assessing the complex sponge microbiota: core, variable and species-specific bacterial communities in marine sponges. ISME J. 2012;6:564–76.

    CAS  PubMed  Google Scholar 

  16. Lee HS, Kwon KK, Kang SG, Cha S-S, Kim S-J, Lee J-H. Approaches for novel enzyme discovery from marine environments. Curr Opin Biotechnol. 2010;21:353–7.

    CAS  PubMed  Google Scholar 

  17. Romano G, Costantini M, Sansone C, Lauritano C, Ruocco N, Ianora A. Marine microorganisms as a promising and sustainable source of bioactive molecules. Mar Environ Res. 2017;128:58–69.

    CAS  PubMed  Google Scholar 

  18. Newman DJ. Predominately uncultured microbes as sources of bioactive agents. Front Microbiol. 2016;7:1832.

    PubMed  PubMed Central  Google Scholar 

  19. Macintyre L, Zhang T, Viegelmann C, Martinez IJ, Cheng C, Dowdells C, et al. Metabolomic tools for secondary metabolite discovery from marine microbial symbionts. Mar Drugs. 2014;12:3416–48.

    PubMed  PubMed Central  Google Scholar 

  20. Abdelmohsen UR, Bayer K, Hentschel U. Diversity, abundance and natural products of marine sponge-associated actinomycetes. Nat Prod Rep. 2014;31:381–99.

    CAS  PubMed  Google Scholar 

  21. Bull AT, Stach JEM. Marine actinobacteria: new opportunities for natural product search and discovery. Trends Microbiol. 2007;15:491–9.

    CAS  PubMed  Google Scholar 

  22. Wright GD. Antibiotics: a new hope. Chem Biol. 2012;19:3–10.

    CAS  PubMed  Google Scholar 

  23. Fischbach MA, Walsh CT. Antibiotics for emerging pathogens. Science. 2009;325:1089–93.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Davies J, Davies D. Origins and evolution of antibiotic resistance. Microbiol Mol Biol Rev. 2010;74:417–33.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Fenical W, Jensen PR. Developing a new resource for drug discovery: marine actinomycete bacteria. Nat Chem Biol. 2006;2:666–73.

    CAS  PubMed  Google Scholar 

  26. Jensen P, Fenical W. Strategies for the discovery of secondary metabolites from marine bacteria: ecological perspectives. Annu Rev Microbiol. 1994;48:559–84.

    CAS  PubMed  Google Scholar 

  27. Freeman MF, Vagstad AL, Piel J. Polytheonamide biosynthesis showcasing the metabolic potential of sponge-associated uncultivated ‘Entotheonella’ bacteria. Curr Opin Chem Biol. 2016;31:8–14.

    CAS  PubMed  Google Scholar 

  28. Senthilkumar K, Kim S-K. Marine invertebrate natural products for anti-inflammatory and chronic diseases. Evid-Based Compl Alt Med. 2013;2013.

  29. Tsukimoto M, Nagaoka M, Shishido Y, Fujimoto J, Nishisaka F, Matsumoto S, et al. Bacterial production of the tunicate-derived antitumor cyclic depsipeptide didemnin B. J Nat Prod. 2011;74:2329–31.

    CAS  PubMed  Google Scholar 

  30. Mehbub MF, Lei J, Franco C, Zhang W. Marine sponge derived natural products between 2001 and 2010: trends and opportunities for discovery of bioactives. Mar Drugs. 2014;12:4539–77.

    PubMed  PubMed Central  Google Scholar 

  31. Munro MHG, Blunt JW, Dumdei EJ, Hickford SJH, Lill RE, Li S, et al. The discovery and development of marine compounds with pharmaceutical potential. Prog Ind Microbiol. 1999;35:15–25.

    CAS  Google Scholar 

  32. Waters AL, Peraud O, Kasanah N, Sims JW, Kothalawala N, Anderson MA, et al. An analysis of the sponge Acanthostrongylophora igens’ microbiome yields an actinomycete that produces the natural product manzamine A. Front Mar Sci. 2014;1:54.

    PubMed  PubMed Central  Google Scholar 

  33. Mohamed NM, Rao V, Hamann MT, Kelly M, Hill RT. Monitoring bacterial diversity of the marine sponge Ircinia strobilina upon transfer into aquaculture. Appl Environ Microbiol. 2008;74:4133–43.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Jeewon R, Luckhun AB, Bhoyroo V, Sadeer NB, Mahomoodally MF, Rampadarath S, et al. Pharmaceutical potential of marine fungal endophytes. In: Jha S, editor. Endophytes and secondary metabolites. Reference series in phytochemistry. Springer; 2019. p. 1–23.

  35. Sun W, Wu W, Liu X, Zaleta-Pinet DA, Clark BR. Bioactive compounds isolated from marine-derived microbes in China: 2009-18. Mar Drugs. 2019;17:339.

    CAS  PubMed Central  Google Scholar 

  36. Wang R, Seyedsayamdost MR. Roseochelin B, an algaecidal natural product synthesized by the Roseobacter Phaeobacter inhibens in response to algal sinapic acid. Org Lett. 2017;19:5138–41.

    CAS  PubMed  Google Scholar 

  37. Li Z-X, Wang X-F, Ren G-W, Yuan X-L, Deng N, Ji G-X, et al. Prenylated diphenyl ethers from the marine algal-derived endophytic fungus Aspergillus tennesseensis. Molecules. 2018;23:2368.

    PubMed Central  Google Scholar 

  38. Zou J-X, Song Y-P, Ji N-Y. Deoxytrichodermaerin, a harziane lactone from the marine algicolous fungus Trichoderma longibrachiatum A-WH-20-2. Nat Prod Res. 2019:1–6.

  39. Song Y-P, Shi Z-Z, Miao F-P, Fang S-T, Yin X-L, Ji N-Y. Tricholumin A, a highly transformed ergosterol derivative from the alga-endophytic fungus Trichoderma asperellum. Org Lett. 2018;20:6306–9.

    CAS  PubMed  Google Scholar 

  40. El-Gendy MMAA, Yahya SMM, Hamed AR, Soltan MM, El-Bondkly AMA. Phylogenetic analysis and biological evaluation of marine endophytic fungi derived from Red Sea sponge Hyrtios erectus. Appl Biochem Biotechnol. 2018;185:755–77.

    CAS  PubMed  Google Scholar 

  41. Suryanarayanan TS, Thirunavukkarasu N, Govindarajulu MB, Sasse F, Jansen R, Murali TS. Fungal endophytes and bioprospecting. Fungal Biol Rev. 2009;23:9–19.

    Google Scholar 

  42. Xu L, Meng W, Cao C, Wang J, Shan W, Wang Q. Antibacterial and antifungal compounds from marine fungi. Mar Drugs. 2015;13:3479–513.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Haygood MG, Schmidt EW, Davidson SK, Faulkner DJ. Microbial symbionts of marine invertebrates: opportunities for microbial biotechnology. J Mol Microbiol Biotechnol. 1999;1:33–43.

    CAS  PubMed  Google Scholar 

  44. Rinkevich B. Cell cultures from marine invertebrates: obstacles, new approaches and recent improvements. J Biotechnol. 1999;70:133–53.

    CAS  Google Scholar 

  45. Bishara A, Rudi A, Goldberg I, Benayahu Y, Kashman Y. Novaxenicins A–D and xeniolides I–K, seven new diterpenes from the soft coral Xenia novaebrittanniae. Tetrahedron. 2006;62:12092–7.

    CAS  Google Scholar 

  46. Hamel C, Prusov EV, Gertsch J, Schweizer WB, Altmann K-H. Total synthesis of the marine diterpenoid blumiolide C. Angew Chem, Int Ed. 2008;47:10081–5.

    CAS  Google Scholar 

  47. Sata NU, Sugano M, Matsunaga S, Fusetani N. Sinulamide: an H, K-ATPase inhibitor from a soft coral Sinularia sp. Tetrahedron Lett. 1999;40:719–22.

    CAS  Google Scholar 

  48. Sung P-J, Chen Y-P, Hwang T-L, Hu W-P, Fang L-S, Wu Y-C, et al. Briaexcavatins C–F, four new briarane-related diterpenoids from the Formosan octocoral Briareum excavatum (Briareidae). Tetrahedron. 2006;62:5686–91.

    CAS  Google Scholar 

  49. Rocha J, Peixe L, Gomes NCM, Calado R. Cnidarians as a source of new marine bioactive compounds—an overview of the last decade and future steps for bioprospecting. Mar Drugs. 2011;9:1860–86.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Zhukova NV. Fatty acids of marine mollusks: Impact of diet, bacterial symbiosis and biosynthetic potential. Biomolecules. 2019;9:857.

    CAS  PubMed Central  Google Scholar 

  51. Zhukova NV, Kharlamenko VI, Svetashev VI, Rodionov IA. Fatty acids as markers of bacterial symbionts of marine bivalve molluscs. J Exp Mar Biol Ecol. 1992;162:253–63.

    CAS  Google Scholar 

  52. Lopera J, Miller IJ, McPhail KL, Kwan JC. Increased biosynthetic gene dosage in a genome-reduced defensive bacterial symbiont. MSystems. 2017;2.

  53. Liu Q-A, Shao C-L, Gu Y-C, Blum M, Gan L-S, Wang K-L, et al. Antifouling and fungicidal resorcylic acid lactones from the sea anemone-derived fungus Cochliobolus lunatus. J Agric Food Chem. 2014;62:3183–91.

    CAS  PubMed  Google Scholar 

  54. Rao KV, Santarsiero BD, Mesecar AD, Schinazi RF, Tekwani BL, Hamann MT. New manzamine alkaloids with activity against infectious and tropical parasitic diseases from an Indonesian sponge. J Nat Prod. 2003;66:823–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Sakai R, Higa T, Jefford CW, Bernardinelli G. Manzamine A, a novel antitumor alkaloid from a sponge. J Am Chem Soc. 1986;108:6404–5.

    CAS  Google Scholar 

  56. Edrada RA, Proksch P, Wray V, Witte L, Müller WEG, Van Soest RWM. Four new bioactive manzamine-type alkaloids from the Philippine marine sponge Xestospongia ashmorica. J Nat Prod. 1996;59:1056–60.

    CAS  PubMed  Google Scholar 

  57. Nakamura H, Deng S, Kobayashi J, Ohizumi Y, Tomotake Y, Matsuzaki T, et al. Keramamine-A and -B, novel antimicrobial alkaloids from the Okinawan marine sponge Pellina sp. Tetrahedron Lett. 1987;28:621–4.

    CAS  Google Scholar 

  58. Ang KKH, Holmes MJ, Higa T, Hamann MT, Kara UAK. In vivo antimalarial activity of the beta-carboline alkaloid manzamine A. Antimicrob Agents Chemother. 2000;44:1645–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. El Sayed KA, Kelly M, Kara UAK, Ang KKH, Katsuyama I, Dunbar DC, et al. New manzamine alkaloids with potent activity against infectious diseases. J Am Chem Soc. 2001;123:1804–8.

    CAS  PubMed  Google Scholar 

  60. Tsuda M, Kobayashi J. Structures and biogenesis of manzamines and related alkaloids. Heterocycles. 1998;46:765–94.

    Google Scholar 

  61. Magnier E, Langlois Y. Manzamine alkaloids, syntheses and synthetic approaches. Tetrahedron. 1998;54:6201–58.

    CAS  Google Scholar 

  62. Yousaf M, El Sayed KA, Rao KV, Lim CW, Hu J-F, Kelly M, et al. 12, 34-Oxamanzamines, novel biocatalytic and natural products from manzamine producing Indo-Pacific sponges. Tetrahedron. 2002;58:7397–402.

    CAS  Google Scholar 

  63. Bibi F, Faheem M, Azhar IE, Yasir M, Alvi SA, Kamal MA, et al. Bacteria from marine sponges: a source of new drugs. Curr Drug Metab. 2017;18:11–15.

    CAS  PubMed  Google Scholar 

  64. Zheng L, Chen H, Han X, Lin W, Yan X. Antimicrobial screening and active compound isolation from marine bacterium NJ6-3-1 associated with the sponge Hymeniacidon perleve. World J Microbiol Biotechnol. 2005;21:201–6.

    CAS  Google Scholar 

  65. Burkholder PR. Studies on antimicrobial substances of sponges I. Isolation, purification, and properties of a new bromine-containing antibacterial substance. J Antibiot. 1967;20:200–3.

    PubMed  Google Scholar 

  66. Pabel CT, Vater J, Wilde C, Franke P, Hofemeister J, Adler B, et al. Antimicrobial activities and matrix-assisted laser desorption/ionization mass spectrometry of Bacillus isolates from the marine sponge Aplysina aerophoba. Mar Biotechnol. 2003;5:424–34.

    CAS  PubMed  Google Scholar 

  67. Carroll AR, Copp BR, Davis RA, Keyzers RA, Prinsep MR. Marine natural products. Nat Prod Rep. 2019;36:122–73.

    CAS  PubMed  Google Scholar 

  68. Marty MJ, Vicente J, Oyler BL, Place A, Hill RT. Sponge symbioses between Xestospongia deweerdtae and Plakortis spp. are not motivated by shared chemical defense against predators. PloS ONE. 2017;12:e0174816.

    PubMed  PubMed Central  Google Scholar 

  69. Agarwal V, Blanton JM, Podell S, Taton A, Schorn MA, Busch J, et al. Metagenomic discovery of polybrominated diphenyl ether biosynthesis by marine sponges. Nat Chem Biol. 2017;13:537–43.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Genilloud O. Actinomycetes: still a source of novel antibiotics. Nat Prod Rep. 2017;34:1203–32.

    CAS  PubMed  Google Scholar 

  71. Ramachandran G, Rajivgandhi G, Maruthupandy M, Manoharan N. Isolation and identification of antibacterial compound from marine endophytic actinomycetes against multi drug resistant bacteria. Ann Microbiol Immunol. 2018;1:1003.

    Google Scholar 

  72. Djinni I, Defant A, Kecha M, Mancini I. Antibacterial polyketides from the marine alga-derived endophitic Streptomyces sundarbansensis: a study on hydroxypyrone tautomerism. Mar Drugs. 2013;11:124–35.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. El-Gendy MMA, Hawas UW, Jaspars M. Novel bioactive metabolites from a marine derived bacterium Nocardia sp. ALAA 2000. J Antibiot. 2008;61:379–86.

    CAS  PubMed  Google Scholar 

  74. Kalinovskaya NI, Kalinovsky AI, Romanenko LA, Dmitrenok PS, Kuznetsova TA. New angucyclines and antimicrobial diketopiperazines from the marine mollusk-derived actinomycete Saccharothrix espanaensis An 113. Nat Prod Commun. 2010;5:597–602.

    CAS  PubMed  Google Scholar 

  75. Rodríguez V, Martín J, Sarmiento-Vizcaíno A, De la Cruz M, García LA, Blanco G, et al. Anthracimycin B, a potent antibiotic against gram-positive bacteria isolated from cultures of the deep-sea actinomycete Streptomyces cyaneofuscatus M-169. Mar Drugs. 2018;16:406.

    PubMed Central  Google Scholar 

  76. Chen M-H, Lian Y-Y, Fang D-S, Chen L, Jia J, Zhang W-L, et al. Identification and antimicrobial properties of a new alkaloid produced by marine-derived Verrucosispora sp. FIM06-0036. Nat Prod Res. 2019:1–7.

  77. Braña AF, Sarmiento-Vizcaíno A, Pérez-Victoria I, Martín J, Otero L, Palacios-Gutiérrez JJ, et al. Desertomycin G, a new antibiotic with activity against Mycobacterium tuberculosis and human breast tumor cell lines produced by Streptomyces althioticus MSM3, isolated from the Cantabrian sea intertidal macroalgae Ulva sp. Mar Drugs. 2019;17:114.

    PubMed Central  Google Scholar 

  78. Rajivgandhi G, Ramachandran G, Maruthupandy M, Saravanakumar S, Manoharan N, Viji R. Antibacterial effect of endophytic actinomycetes from marine algae against multi drug resistant gram negative bacteria. Exam Mar Biol Oceanogr. 2018;1:1–8.

    Google Scholar 

  79. Rajivgandhi G, Muneeswaran T, Maruthupandy M, Ramakritinan CM, Saravanan K, Ravikumar V, et al. Antibacterial and anticancer potential of marine endophytic actinomycetes Streptomyces coeruleorubidus GRG 4 (KY457708) compound against colistin resistant uropathogens and A549 lung cancer cells. Microb Pathog. 2018;125:325–35.

    CAS  PubMed  Google Scholar 

  80. Abdalla MA, Sulieman S, McGaw LJ. Microbial communication: a significant approach for new leads. S Afr J Bot. 2017;113:461–70.

    CAS  Google Scholar 

  81. Kealey C, Creaven CA, Murphy CD, Brady CB. New approaches to antibiotic discovery. Biotechnol Lett. 2017;39:805–17.

    CAS  PubMed  Google Scholar 

  82. Yang S-Q, Li X-M, Li X, Li H-L, Meng L-H, Wang B-G. New citrinin analogues produced by coculture of the marine algal-derived endophytic fungal strains Aspergillus sydowii EN-534 and Penicillium citrinum EN-535. Phytochem Lett. 2018;25:191–5.

    CAS  Google Scholar 

  83. Kaul S, Gupta S, Ahmed M, Dhar MK. Endophytic fungi from medicinal plants: a treasure hunt for bioactive metabolites. Phytochem Rev. 2012;11:487–505.

    CAS  Google Scholar 

  84. Wani ZA, Ashraf N, Mohiuddin T, Riyaz-Ul-Hassan S. Plant-endophyte symbiosis, an ecological perspective. Appl Microbiol Biotechnol. 2015;99:2955–65.

    CAS  PubMed  Google Scholar 

  85. Parekh J, Chanda S. Antibacterial and phytochemical studies on twelve species of Indian medicinal plants. Afr J Biomed Res. 2007;10:175–81.

    Google Scholar 

  86. Cheesman MJ, Ilanko A, Blonk B, Cock IE. Developing new antimicrobial therapies: are synergistic combinations of plant extracts/compounds with conventional antibiotics the solution? Pharmacogn Rev. 2017;11:57–72.

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Duraipandiyan V, Raja TW, Al-Dhabi NA, Savarimuthu I. Antimicrobial properties of traditional medicinal plants: status and potential. In: Goyal MR, Chauhan DN, editors. Plant- and marine-based phytochemicals for human health: attributes, potential, and use. CRC Press; 2018. p. 33–60.

  88. Rao SR, Ravishankar GA. Plant cell cultures: chemical factories of secondary metabolites. Biotechnol Adv. 2002;20:101–53.

    CAS  PubMed  Google Scholar 

  89. Cowan MM. Plant products as antimicrobial agents. Clin Microbiol Rev. 1999;12:564–82.

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Zakaria ZA, Rofiee MS, Mohamed AM, Teh LK, Salleh MZ. In vitro antiproliferative and antioxidant activities and total phenolic contents of the extracts of Melastoma malabathricum leaves. J Acupunct Meridian Stud. 2011;4:248–56.

    CAS  PubMed  Google Scholar 

  91. Ibrahim MA, Mansoor AA, Gross A, Ashfaq MK, Jacob M, Khan SI, et al. Methicillin-resistant Staphylococcus aureus (MRSA)-active metabolites from Platanus occidentalis (American sycamore). J Nat Prod. 2009;72:2141–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Nakayama M, Shimatani K, Ozawa T, Shigemune N, Tsugukuni T, Tomiyama D, et al. A study of the antibacterial mechanism of catechins: isolation and identification of Escherichia coli cell surface proteins that interact with epigallocatechin gallate. Food Control. 2013;33:433–9.

    CAS  Google Scholar 

  93. Miklasińska M, Kępa M, Wojtyczka RD, Idzik D, Dziedzic A, Wąsik TJ. Catechin hydrate augments the antibacterial action of selected antibiotics against Staphylococcus aureus clinical strains. Molecules. 2016;21:244.

    PubMed  PubMed Central  Google Scholar 

  94. Marchese A, Barbieri R, Coppo E, Orhan IE, Daglia M, Nabavi SF, et al. Antimicrobial activity of eugenol and essential oils containing eugenol: A mechanistic viewpoint. Crit Rev Microbiol. 2017;43:668–89.

    CAS  PubMed  Google Scholar 

  95. Xu J-G, Liu T, Hu Q-P, Cao X-M. Chemical composition, antibacterial properties and mechanism of action of essential oil from clove buds against Staphylococcus aureus. Molecules. 2016;21:1194.

    PubMed Central  Google Scholar 

  96. Qiu J, Feng H, Lu J, Xiang H, Wang D, Dong J, et al. Eugenol reduces the expression of virulence-related exoproteins in Staphylococcus aureus. Appl Environ Microbiol. 2010;76:5846–51.

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Dhara L, Tripathi A. Antimicrobial activity of eugenol and cinnamaldehyde against extended spectrum beta lactamase producing enterobacteriaceae by in vitro and molecular docking analysis. Eur J Integr Med. 2013;5:527–36.

    Google Scholar 

  98. Marcos-Arias C, Eraso E, Madariaga L, Quindós G. In vitro activities of natural products against oral Candida isolates from denture wearers. BMC Complementary Altern Med. 2011;11:119.

    CAS  Google Scholar 

  99. Ahmad A, Khan A, Khan LA, Manzoor N. In vitro synergy of eugenol and methyleugenol with fluconazole against clinical Candida isolates. J Med Microbiol. 2010;59:1178–84.

    CAS  PubMed  Google Scholar 

  100. de Oliveira Pereira F, Mendes JM, de Oliveira Lima E. Investigation on mechanism of antifungal activity of eugenol against Trichophyton rubrum. Med Mycol 2013;51:507–13.

    PubMed  Google Scholar 

  101. Ikram M. A review on the chemical and pharmacological aspects of genus. Berberis Planta Med. 1975;28:353–8.

    CAS  PubMed  Google Scholar 

  102. Neag MA, Mocan A, Echeverría J, Pop RM, Bocsan CI, Crişan G, et al. Berberine: Botanical occurrence, traditional uses, extraction methods, and relevance in cardiovascular, metabolic, hepatic, and renal disorders. Front Pharm. 2018;9:557.

    Google Scholar 

  103. Peng L, Kang S, Yin Z, Jia R, Song X, Li L, et al. Antibacterial activity and mechanism of berberine against Streptococcus agalactiae. Int J Clin Exp Pathol. 2015;8:5217–23.

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Yu H-H, Kim K-J, Cha J-D, Kim H-K, Lee Y-E, Choi N-Y, et al. Antimicrobial activity of berberine alone and in combination with ampicillin or oxacillin against methicillin-resistant Staphylococcus aureus. J Med Food. 2005;8:454–61.

    CAS  PubMed  Google Scholar 

  105. Kim W-S, Choi WJ, Lee S, Kim WJ, Lee DC, Sohn UD, et al. Anti-inflammatory, antioxidant and antimicrobial effects of artemisinin extracts from Artemisia annua L. Korean J Physiol Pharm. 2015;19:21–27.

    CAS  Google Scholar 

  106. Appalasamy S, Lo KY, Ch’ng SJ, Nornadia K, Othman AS, Chan L-K. Antimicrobial activity of artemisinin and precursor derived from in vitro plantlets of Artemisia annua L. BioMed Res Int. 2014;2014.

  107. Macé S, Hansen LT, Rupasinghe HPV. Anti-bacterial activity of phenolic compounds against Streptococcus pyogenes. Medicines. 2017;4:25.

    PubMed Central  Google Scholar 

  108. Kowalski KP, Bacon C, Bickford W, Braun H, Clay K, Leduc-Lapierre M, et al. Advancing the science of microbial symbiosis to support invasive species management: a case study on Phragmites in the Great Lakes. Front Microbiol. 2015;6:95.

    PubMed  PubMed Central  Google Scholar 

  109. Tanaka Y, Hosaka T, Ochi K. Rare earth elements activate the secondary metabolite–biosynthetic gene clusters in Streptomyces coelicolor A3(2). J Antibiot. 2010;63:477–81.

    CAS  PubMed  Google Scholar 

  110. Traxler MF, Seyedsayamdost MR, Clardy J, Kolter R. Interspecies modulation of bacterial development through iron competition and siderophore piracy. Mol Microbiol. 2012;86:628–44.

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Bhardwaj C, Cui Y, Hofstetter T, Liu SY, Bernstein HC, Carlson RP, et al. Differentiation of microbial species and strains in coculture biofilms by multivariate analysis of laser desorption postionization mass spectra. Analyst. 2013;138:6844–51.

    CAS  PubMed  PubMed Central  Google Scholar 

  112. Bertrand S, Schumpp O, Bohni N, Bujard A, Azzollini A, Monod M, et al. Detection of metabolite induction in fungal co-cultures on solid media by high-throughput differential ultra-high pressure liquid chromatography–time-of-flight mass spectrometry fingerprinting. J Chromatogr A. 2013;1292:219–28.

    CAS  PubMed  Google Scholar 

  113. Du J, Zhou J, Xue J, Song H, Yuan Y. Metabolomic profiling elucidates community dynamics of the Ketogulonicigenium vulgare–Bacillus megaterium consortium. Metabolomics. 2012;8:960–73.

    CAS  Google Scholar 

  114. Derewacz DK, Covington BC, McLean JA, Bachmann BO. Mapping microbial response metabolomes for induced natural product discovery. ACS Chem Biol. 2015;10:1998–2006.

    CAS  PubMed  PubMed Central  Google Scholar 

  115. Goodwin CR, Covington BC, Derewacz DK, McNees CR, Wikswo JP, McLean JA, et al. Structuring microbial metabolic responses to multiplexed stimuli via self-organizing metabolomics maps. Chem Biol. 2015;22:661–70.

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Goodwin CR, Sherrod SD, Marasco CC, Bachmann BO, Schramm-Sapyta N, Wikswo JP, et al. Phenotypic mapping of metabolic profiles using self-organizing maps of high-dimensional mass spectrometry data. Anal Chem. 2014;86:6563–71.

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Watrous J, Roach P, Alexandrov T, Heath BS, Yang JY, Kersten RD, et al. Mass spectral molecular networking of living microbial colonies. Proc Natl Acad Sci USA. 2012;109:E1743–52.

    CAS  PubMed  Google Scholar 

  118. Yang JY, Sanchez LM, Rath CM, Liu X, Boudreau PD, Bruns N, et al. Molecular networking as a dereplication strategy. J Nat Prod. 2013;76:1686–99.

    CAS  PubMed  PubMed Central  Google Scholar 

  119. Kersten RD, Yang Y-L, Xu Y, Cimermancic P, Nam S-J, Fenical W, et al. A mass spectrometry-guided genome mining approach for natural product peptidogenomics. Nat Chem Biol. 2011;7:794–802.

    CAS  PubMed  PubMed Central  Google Scholar 

  120. Liu W-T, Lamsa A, Wong WR, Boudreau PD, Kersten R, Peng Y, et al. MS/MS-based networking and peptidogenomics guided genome mining revealed the stenothricin gene cluster in Streptomyces roseosporus. J Antibiot. 2014;67:99–104.

    CAS  PubMed  Google Scholar 

  121. Bibb MJ. Regulation of secondary metabolism in streptomycetes. Curr Opin Microbiol. 2005;8:208–15.

    CAS  PubMed  Google Scholar 

  122. Hopwood DA. How do antibiotic‐producing bacteria ensure their self‐resistance before antibiotic biosynthesis incapacitates them? Mol Microbiol. 2007;63:937–40.

    CAS  PubMed  Google Scholar 

  123. Davies J, Spiegelman GB, Yim G. The world of subinhibitory antibiotic concentrations. Curr Opin Microbiol. 2006;9:445–53.

    CAS  PubMed  Google Scholar 

  124. Yim G, Wang HH, Davies J. Antibiotics as signalling molecules. Philos Trans R Soc, B. 2007;362:1195–1200.

    CAS  Google Scholar 

  125. Imai Y, Sato S, Tanaka Y, Ochi K, Hosaka T. Lincomycin at subinhibitory concentrations potentiates secondary metabolite production by Streptomyces spp. Appl Environ Microbiol. 2015;81:3869–79.

    CAS  PubMed  PubMed Central  Google Scholar 

  126. Netzker T, Fischer J, Weber J, Mattern DJ, König CC, Valiante V, et al. Microbial communication leading to the activation of silent fungal secondary metabolite gene clusters. Front Microbiol. 2015;6:299.

    PubMed  PubMed Central  Google Scholar 

  127. Macheleidt J, Mattern DJ, Fischer J, Netzker T, Weber J, Schroeckh V, et al. Regulation and role of fungal secondary metabolites. Annu Rev Genet. 2016;50:371–92.

    CAS  PubMed  Google Scholar 

  128. Andersen RJ. Sponging off nature for new drug leads. Biochem Pharmacol. 2017;139:3–14.

    CAS  PubMed  Google Scholar 

  129. Sagar S, Kaur M, Minneman KP. Antiviral lead compounds from marine sponges. Mar Drugs. 2010;8:2619–38.

    CAS  PubMed  PubMed Central  Google Scholar 

  130. Brinkmann CM, Marker A, Kurtböke DI. An overview on marine sponge-symbiotic bacteria as unexhausted sources for natural product discovery. Diversity. 2017;9:40.

    Google Scholar 

  131. Pandey S, Sree A, Dash SS, Sethi DP, Chowdhury L. Diversity of marine bacteria producing beta-glucosidase inhibitors. Microb Cell Fact. 2013;12:35.

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Epstein SS. The phenomenon of microbial uncultivability. Curr Opin Microbiol. 2013;16:636–42.

    CAS  PubMed  Google Scholar 

  133. Bhatnagar I, Kim S-K. Immense essence of excellence: Marine microbial bioactive compounds. Mar Drugs. 2010;8:2673–701.

    CAS  PubMed  PubMed Central  Google Scholar 

  134. Leal MC, Calado R, Sheridan C, Alimonti A, Osinga R. Coral aquaculture to support drug discovery. Trends Biotechnol. 2013;31:555–61.

    CAS  PubMed  Google Scholar 

  135. Leal MC, Calado R. Marine natural products: biodiscovery, biodiversity, and bioproduction. In: Brahmachari G, editor. Bioactive natural products: chemistry and biology. Hoboken: Wiley Online Library; 2015. p. 473–90.

  136. Leal MC, Sheridan C, Osinga R, Dionísio G, Rocha RJM, Silva B, et al. Marine microorganism-invertebrate assemblages: perspectives to solve the “supply problem” in the initial steps of drug discovery. Mar Drugs. 2014;12:3929–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  137. Sweet MJ, Bulling MT. On the importance of the microbiome and pathobiome in coral health and disease. Front Mar Sci. 2017;4:9.

    Google Scholar 

  138. Sweet MJ, Smith D, Bythell JC, Craggs J. Changes in microbial diversity associated with two coral species recovering from a stressed state in a public aquarium system. J Zoo Aquar Res. 2013;1:52–60.

    Google Scholar 

  139. Trindade M, van Zyl LJ, Navarro-Fernández J, Abd Elrazak A. Targeted metagenomics as a tool to tap into marine natural product diversity for the discovery and production of drug candidates. Front Microbiol. 2015;6:890.

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This study was provided by Abney Foundation, the Charles and Carol Cooper Endowment, and the South Carolina SmartState Programs and funding from NCCIH.

Author information

Authors and Affiliations

  1. Analytical Development Department, Cambrex Pharmaceuticals, Charles City, IA, USA

    Vedanjali Gogineni

  2. Department of Drug Discovery, Biomedical Sciences and Public Health, College of Pharmacy and Medicine, Medical University of South Carolina, Charleston, SC, USA

    Vedanjali Gogineni, Xiaoyan Chen, George Hanna & Mark T. Hamann

  3. Department of Pharmaceutical Biology, Faculty of Pharmacy, University of Gadjah Mada, Yogyakarta, Indonesia

    Dian Mayasari

Authors
  1. Vedanjali Gogineni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiaoyan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. George Hanna
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dian Mayasari
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mark T. Hamann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mark T. Hamann.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Dedicated to Professor William Fenical in recognition of his contributions to marine derived secondary metabolites.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gogineni, V., Chen, X., Hanna, G. et al. Role of symbiosis in the discovery of novel antibiotics. J Antibiot 73, 490–503 (2020). https://doi.org/10.1038/s41429-020-0321-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41429-020-0321-6

This article is cited by

Search

Advanced search

Quick links