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Biology and applications of co-produced, synergistic antimicrobials from environmental bacteria

Nature Microbiology volume 6, pages 1118–1128 (2021)Cite this article

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Abstract

Environmental bacteria, such as Streptomyces spp., produce specialized metabolites that are potent antibiotics and therapeutics. Selected specialized antimicrobials are co-produced and function together synergistically. Co-produced antimicrobials comprise multiple chemical classes and are produced by a wide variety of bacteria in different environmental niches, suggesting that their combined functions are ecologically important. Here, we highlight the exquisite mechanisms that underlie the simultaneous production and functional synergy of 16 sets of co-produced antimicrobials. To date, antibiotic and antifungal discovery has focused mainly on single molecules, but we propose that methods to target co-produced antimicrobials could widen the scope and applications of discovery programs.

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Fig. 1: Synergistic mechanisms of action and the biosynthetic strategies for the production of synergistic antimicrobials.
Fig. 2: Synergistic binding to the same target, the ribosome, by streptogramins and lankacidin and lankamycin.
Fig. 3: Inhibition of two targets in the same pathway, a Slt and a Pbp, by bulgecin and sulfazecin.
Fig. 4: Synergism through a two-step membrane attack—lacticin A1 binds to lipid II and then enables the binding of lacticin A2 and pore formation.
Fig. 5: Synergism through enhanced delivery; cyclodextrins may help to solubilize anabaenolysins and provide access to the fungal membrane through extraction of ergosterol.

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Acknowledgements

We thank S. Tan, M. Lefebvre and S. Pimentel-Elardo for comments on the manuscript. Figures were created with Biorender.com. This work was supported by the Canadian Institutes of Health Research (MID-406688, to J.R.N.).

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  1. Department of Biochemistry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

    Kirsten J. Meyer & Justin R. Nodwell

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Meyer, K.J., Nodwell, J.R. Biology and applications of co-produced, synergistic antimicrobials from environmental bacteria. Nat Microbiol 6, 1118–1128 (2021). https://doi.org/10.1038/s41564-021-00952-6

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