In recent years, research in the field of Microbial Ecology has revealed the tremendous diversity and complexity of microbial communities across different ecosystems. Microbes play a major role in ecosystem functioning and contribute to the health and fitness of higher organisms. Scientists are now facing many technological and methodological challenges in analyzing these complex natural microbial communities. The advances in analytical and omics techniques have shown that microbial communities are largely shaped by chemical interaction networks mediated by specialized (water-soluble and volatile) metabolites. However, studies concerning microbial chemical interactions need to consider biotic and abiotic factors on multidimensional levels, which require the development of new tools and approaches mimicking natural microbial habitats. In this review, we describe environmental factors affecting the production and transport of specialized metabolites. We evaluate their ecological functions and discuss approaches to address future challenges in microbial chemical ecology (MCE). We aim to emphasize that future developments in the field of MCE will need to include holistic studies involving organisms at all levels and to consider mechanisms underlying the interactions between viruses, micro-, and macro-organisms in their natural environments.
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Hartmann T. The lost origin of chemical ecology in the late 19th century. Proc Natl Acad Sci USA. 2008;105:4541–6.
Bassler BL. How bacteria talk to each other: regulation of gene expression by quorum sensing. Curr Opin Microbiol. 1999;2:582–7.
Bassler BL, Greenberg EP, Stevens AM. Cross-species induction of luminescence in the quorum-sensing bacterium Vibrio harveyi. J Bacteriol. 1997;179:4043–5.
Atkinson S, Williams P. Quorum sensing and social networking in the microbial world. J R Soc Interface. 2009;6:959–78.
Mithofer A, Boland W. Do you speak chemistry? Small chemical compounds represent the evolutionary oldest form of communication between organisms. EMBO Rep. 2016;17:626–9.
Davies J. Specialized microbial metabolites: functions and origins. J Antibiot. 2013;66:361–4.
Tyc O, Song C, Dickschat JS, Vos M, Garbeva P. The ecological role of volatile and soluble secondary metabolites produced by soil bacteria. Trends Microbiol. 2017;25:280–92.
Riclea R, Aigle B, Leblond P, Schoenian I, Spiteller D, Dickschat JS. Volatile lactones from streptomycetes arise via the antimycin biosynthetic pathway. Chembiochem. 2012;13:1635–44.
Hanzel J, Harms H, Wick LY. Bacterial chemotaxis along vapor-phase gradients of naphthalene. Environ Sci Technol. 2010;44:9304–10.
Schmidt R, Cordovez V, de Boer W, Raaijmakers J, Garbeva P. Volatile affairs in microbial interactions. ISME J. 2015;9:2329–35.
Schulz-Bohm K, Gerards S, Hundscheid M, Melenhorst J, de Boer W, Garbeva P. Calling from distance: attraction of soil bacteria by plant root volatiles. ISME J. 2018;12:1252–62.
Fink P. Ecological functions of volatile organic compounds in aquatic systems. Marine and Freshwater Behaviour and Physiology. 2007;40:155–68.
Groenhagen U, Leandrini De Oliveira AL, Fielding E, Moore BS, Schulz S. Coupled Biosynthesis of Volatiles and Salinosporamide A in Salinispora tropica. Chembiochem. 2016;17:1978–85.
Harig T, Schlawis C, Ziesche L, Pohlner M, Engelen B, Schulz S. Nitrogen-containing volatiles from marine salinispora pacifica and roseobacter-group bacteria. J Nat Prod. 2017;80:3289–95.
Thiel V, Brinkhoff T, Dickschat JS, Wickel S, Grunenberg J, Wagner-Dobler I, et al. Identification and biosynthesis of tropone derivatives and sulfur volatiles produced by bacteria of the marine Roseobacter clade. Org Biomol Chem. 2010;8:234–46.
Wheatley RE. The consequences of volatile organic compound mediated bacterial and fungal interactions. Antonie Van Leeuwenhoek. 2002;81:357–64.
Avalos M, van Wezel GP, Raaijmakers JM, Garbeva P. Healthy scents: microbial volatiles as new frontier in antibiotic research? Curr Opin Microbiol. 2018;45:84–91.
Hemaiswarya S, Doble M. Synergistic interaction of eugenol with antibiotics against Gram negative bacteria. Phytomedicine. 2009;16:997–1005.
Khalil ZG, Cruz-Morales P, Licona-Cassani C, Marcellin E, Capon RJ. Inter-kingdom beach warfare: microbial chemical communication activates natural chemical defences. ISME J. 2019;13:147–58.
Sasaki Y, Oguchi H, Kobayashi T, Kusama S, Sugiura R, Moriya K, et al. Nitrogen oxide cycle regulates nitric oxide levels and bacterial cell signaling. Sci Rep. 2016;6:22038.
Bode HB, Bethe B, Hofs R, Zeeck A. Big effects from small changes: possible ways to explore nature’s chemical diversity. Chembiochem. 2002;3:619–27.
Romano S, Jackson SA, Patry S, Dobson ADW. Extending the “One Strain Many Compounds” (OSMAC) principle to marine microorganisms. Mar Drugs. 2018;16:E244.
Locatelli FM, Goo KS, Ulanova D. Effects of trace metal ions on secondary metabolism and the morphological development of streptomycetes. Metallomics. 2016;8:469–80.
van der Heul HU, Bilyk BL, McDowall KJ, Seipke RF, van Wezel GP. Regulation of antibiotic production in Actinobacteria: new perspectives from the post-genomic era. Nat Prod Rep. 2018;35:575–604.
Gonzalez I, Niebla A, Lemus M, Gonzalez L, Iznaga IO, Perez ME, et al. Ecological approach of macrolide-lincosamides-streptogramin producing actinomyces from Cuban soils. Lett Appl Microbiol. 1999;29:147–50.
Sagova-Mareckova M, Ulanova D, Sanderova P, Omelka M, Kamenik Z, Olsovska J, et al. Phylogenetic relatedness determined between antibiotic resistance and 16S rRNA genes in actinobacteria. BMC Microbiol. 2015;15:81.
Garbeva P, Tyc O, Remus-Emsermann MN, van der Wal A, Vos M, Silby M, et al. No apparent costs for facultative antibiotic production by the soil bacterium Pseudomonas fluorescens Pf0-1. PLoS One. 2011;6:e27266.
Daniel-Ivad M, Pimentel-Elardo S, Nodwell JR. Control of specialized metabolism by signaling and transcriptional regulation: opportunities for new platforms for drug discovery? Annu Rev Microbiol. 2018;72:25–48.
Miller MB, Bassler BL. Quorum sensing in bacteria. Annu Rev Microbiol. 2001;55:165–99.
Nguyen TB, Kitani S, Shimma S, Nihira T. Butenolides from Streptomyces albus J1074 act as external signals to stimulate avermectin production in Streptomyces avermitilis. Appl Environ Microbiol. 2018;84:e02791–17.
Ryan RP, Dow JM. Diffusible signals and interspecies communication in bacteria. Microbiology. 2008;154:1845–58.
Onaka H, Mori Y, Igarashi Y, Furumai T. Mycolic acid-containing bacteria induce natural-product biosynthesis in Streptomyces species. Appl Environ Microbiol. 2011;77:400–6.
Asamizu S, Ozaki T, Teramoto K, Satoh K, Onaka H. Killing of mycolic acid-containing bacteria aborted induction of antibiotic production by streptomyces in combined-culture. PLoS One. 2015;10:e0142372.
Abdelmohsen UR, Grkovic T, Balasubramanian S, Kamel MS, Quinn RJ, Hentschel U. Elicitation of secondary metabolism in actinomycetes. Biotechnol Adv. 2015;33:798–811.
Zhu H, Sandiford SK, van Wezel GP. Triggers and cues that activate antibiotic production by actinomycetes. J Ind Microbiol Biotechnol. 2014;41:371–86.
Semple KT, Doick KJ, Wick LY, Harms H. Microbial interactions with organic contaminants in soil: Definitions, processes and measurement. Environmental Pollution. 2007;150:166–76.
Ortega-Calvo JJ, Harmsen J, Parsons JR, Semple KT, Aitken MD, Ajao C, et al. From bioavailability science to regulation of organic chemicals. Environ Sci Technol. 2015;49:10255–64.
Johnsen AR, Wick LY, Harms H. Principles of microbial PAH-degradation in soil. Environ Pollut. 2005;133:71–84.
Raynaud X, Nunan N. Spatial ecology of bacteria at the microscale in soil. PLoS One. 2014;9:e87217.
Gantner S, Schmid M, Durr C, Schuhegger R, Steidle A, Hutzler P, et al. In situ quantitation of the spatial scale of calling distances and population density-independent N-acylhomoserine lactone-mediated communication by rhizobacteria colonized on plant roots. FEMS Microbiol Ecol. 2006;56:188–94.
Tecon R, Or D. Biophysical processes supporting the diversity of microbial life in soil. FEMS Microbiol Rev. 2017;41:599–623.
Schmidt R, Etalo DW, de Jager V, Gerards S, Zweers H, de Boer W, et al. Microbial small talk: volatiles in fungal–bacterial interactions. Front Microbiol. 2016;6:12.
Barto EK, Weidenhamer JD, Cipollini D, Rillig MC. Fungal superhighways: do common mycorrhizal networks enhance below ground communication? Trends Plant Sci. 2012;17:633–7.
Worrich A, Stryhanyuk H, Musat N, Konig S, Banitz T, Centler F, et al. Mycelium-mediated transfer of water and nutrients stimulates bacterial activity in dry and oligotrophic environments. Nat Commun. 2017;8:15472.
Furuno S, Foss S, Wild E, Jones KC, Semple KT, Harms H, et al. Mycelia promote active transport and spatial dispersion of polycyclic aromatic hydrocarbons. Environ Sci Technol. 2012;46:5463–70.
Torres-Cortes G, Ghignone S, Bonfante P, Schussler A. Mosaic genome of endobacteria in arbuscular mycorrhizal fungi: transkingdom gene transfer in an ancient mycoplasma-fungus association. Proc Natl Acad Sci USA. 2015;112:7785–90.
Deveau A, Bonito G, Uehling J, Paoletti M, Becker M, Bindschedler S, et al. Bacterial-fungal interactions: ecology, mechanisms and challenges. FEMS Microbiol Rev. 2018;42:335–52.
Kohlmeier S, Smits TH, Ford RM, Keel C, Harms H, Wick LY. Taking the fungal highway: mobilization of pollutant-degrading bacteria by fungi. Environ Sci Technol. 2005;39:4640–6.
Berthold T, Centler F, Hubschmann T, Remer R, Thullner M, Harms H, et al. Mycelia as a focal point for horizontal gene transfer among soil bacteria. Sci Rep. 2016;6:36390.
Pratama AA, van Elsas JD. A novel inducible prophage from the mycosphere inhabitant Paraburkholderia terrae BS437. Sci Rep. 2017;7:9156.
Zhang M, Visser S, Pereira e Silva MC, van Elsas JD. IncP-1 and PromA group plasmids are major providers of horizontal gene transfer capacities across bacteria in the mycosphere of different soil fungi. Microb Ecol. 2015;69:169–79.
Nett M, Ikeda H, Moore BS. Genomic basis for natural product biosynthetic diversity in the actinomycetes. Nat Prod Rep. 2009;26:1362–84.
Romero D, Traxler MF, Lopez D, Kolter R. Antibiotics as signal molecules. Chem Rev. 2011;111:5492–505.
Traxler MF, Kolter R. Natural products in soil microbe interactions and evolution. Nat Prod Rep. 2015;32:956–70.
Davies J, Spiegelman GB, Yim G. The world of subinhibitory antibiotic concentrations. Curr Opin Microbiol. 2006;9:445–53.
De Nobili M, Contin M, Mondini C, Brookes PC. Soil microbial biomass is triggered into activity by trace amounts of substrate. Soil Biol Biochem. 2001;33:1163–70.
Abisado RG, Benomar S, Klaus JR, Dandekar AA, Chandler JR. Bacterial quorum sensing and microbial community interactions. MBio. 2018;8. https://doi.org/10.1128/mBio.02331-17.
Brameyer S, Bode HB, Heermann R. Languages and dialects: bacterial communication beyond homoserine lactones. Trends Microbiol. 2015;23:521–3.
Stasulli NM, Shank EA. Profiling the metabolic signals involved in chemical communication between microbes using imaging mass spectrometry. FEMS Microbiol Rev. 2016;40:807–13.
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.
Shank EA. Considering the lives of microbes in microbial communities. mSystems. 2018;3:e00155–17.
Patin NV, Schorn M, Aguinaldo K, Lincecum T, Moore BS, Jensen PR. Effects of actinomycete secondary metabolites on sediment microbial communities. Appl Environ Microbiol. 2017;83:e02331.
Connell JL, Ritschdorff ET, Whiteley M, Shear JB. 3D printing of microscopic bacterial communities. Proc Natl Acad Sci USA. 2013;110:18380–5.
Rangel DP, Superak C, Bielschowsky M, Farris K, Falconer RE, Baveye PC. Rapid prototyping and 3-D printing of experimental equipment in soil science research. Soil Sci Soc Am J. 2013;77:54–59.
Borer BAM, Hatzimanikatis V, Or D. Integrating metabolic networks into an individual based model of bacterial life in soil (conference poster). ISME17. 2018.; pp 1.
Aleklett K, Kiers ET, Ohlsson P, Shimizu TS, Caldas VE, Hammer EC. Build your own soil: exploring microfluidics to create microbial habitat structures. ISME J. 2018;12:312–9.
Pessotti RC, Hansen BL, Traxler MF. In search of model ecological systems for understanding specialized metabolism. mSystems. 2018;3:e00175–17.
Erez Z, Steinberger-Levy I, Shamir M, Doron S, Stokar-Avihail A, Peleg Y, et al. Communication between viruses guides lysis-lysogeny decisions. Nature. 2017;541:488–93.
Silpe JE, Bassler BL. A host-produced quorum-sensing autoinducer controls a phage lysis-lysogeny decision. Cell. 2019;176:268–80 e213.
Kronheim S, Daniel-Ivad M, Duan Z, Hwang S, Wong AI, Mantel I, et al. A chemical defence against phage infection. Nature. 2018;564:283–6.
Traxler MF, Kolter R. A massively spectacular view of the chemical lives of microbes. Proc Natl Acad Sci USA 2012;109:10128–9.
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:E1743–1752.
Rosenberg E, Sharon G, Atad I, Zilber-Rosenberg I. The evolution of animals and plants via symbiosis with microorganisms. Environ Microbiol Rep. 2010;2:500–6.
Carrion VJ, Cordovez V, Tyc O, Etalo DW, de Bruijn I, de Jager VCL, et al. Involvement of Burkholderiaceae and sulfurous volatiles in disease-suppressive soils. ISME J. 2018;12:2307–21.
Cordovez V, Carrion VJ, Etalo DW, Mumm R, Zhu H, van Wezel GP, et al. Diversity and functions of volatile organic compounds produced by Streptomyces from a disease-suppressive soil. Front Microbiol. 2015;6:1081.
Joice R, Yasuda K, Shafquat A, Morgan XC, Huttenhower C. Determining microbial products and identifying molecular targets in the human microbiome. Cell Metab. 2014;20:731–41.
The Human Microbiome Project C, Huttenhower C, Gevers D, Knight R, Abubucker S, Badger JH, et al. Structure, function and diversity of the healthy human microbiome. Nature. 2012;486:207.
McDonald JA, Fuentes S, Schroeter K, Heikamp-deJong I, Khursigara CM, de Vos WM, et al. Simulating distal gut mucosal and luminal communities using packed-column biofilm reactors and an in vitro chemostat model. J Microbiol Methods. 2015;108:36–44.
Shah P, Fritz JV, Glaab E, Desai MS, Greenhalgh K, Frachet A, et al. A microfluidics-based in vitro model of the gastrointestinal human-microbe interface. Nat Commun. 2016;7:11535.
The authors would like to thank all participants of the roundtable session “Microbial chemical ecology: intraspecies and interspecies communication” at ISME 17 for the fruitful discussion. We acknowledge funding from the Education, Culture, Sports, Science, and Technology Ministry of Japan special project costs Four-Dimensional Kuroshio Marine Science (4D-KMS) Project and Japan Society for the Promotion of Science (JSPS KAKENHI Grant Number 16K18678) to DU. HBB acknowledges support from the State of Hesse for the LOEWE TBG research center. LYW acknowledges support from the Collaborative Research Centre AquaDiva (CRC 1076 AquaDiva) at the Friedrich Schiller University Jena and the Helmholtz Centre for Environmental Research—UFZ, funded by the Deutsche Forschungsgemeinschaft (DFG). PG acknowledges the Netherlands Organization for Scientific Research (NWO), VIDI personal grant (864.11.015). This is publication 6750 of the NIOO-KNAW.
Conflict of interest
The authors declare that they have no conflict of interest.
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