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The microbiome-shaping roles of bacteriocins

Abstract

The microbiomes on human body surfaces affect health in multiple ways. They include not only commensal or mutualistic bacteria but also potentially pathogenic bacteria, which can enter sterile tissues to cause invasive infection. Many commensal bacteria produce small antibacterial molecules termed bacteriocins that have the capacity to eliminate specific colonizing pathogens; as such, bacteriocins have attracted increased attention as potential microbiome-editing tools. Metagenome-based and activity-based screening approaches have strongly expanded our knowledge of the abundance and diversity of bacteriocin biosynthetic gene clusters and the properties of a continuously growing list of bacteriocin classes. The dynamic acquisition, diversification or loss of bacteriocin genes can shape the fitness of a bacterial strain that is in competition with bacteriocin-susceptible bacteria. However, a bacteriocin can only provide a competitive advantage if its fitness benefit exceeds the metabolic cost of production, if it spares crucial mutualistic partner strains and if major competitors cannot develop resistance. In contrast to most currently available antibiotics, many bacteriocins have only narrow activity ranges and could be attractive agents for precision therapy and prevention of infections. A common scientific strategy involving multiple disciplines is needed to uncover the immense potential of microbiome-shaping bacteriocins.

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Fig. 1: Effects of bacteriocins on microbial community dynamics and composition.
Fig. 2: Examples of small-molecule bacteriocins.
Fig. 3: Antimicrobial mechanisms of bacteriocins.
Fig. 4: Evolution and effects on bacterial fitness of bacteriocin BGC transfer.
Fig. 5: Roles of pathogen-targeting bacteriocins.

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Acknowledgements

The authors thank their co-workers and collaborators for helpful discussion. The authors’ work is financed by grants from Deutsche Forschungsgemeinschaft (DFG) TRR261 (project ID 398967434), GRK1708 and Cluster of Excellence EXC2124 Controlling Microbes to Fight Infection (CMFI) (project ID 390838134) to S.H., H.B.-O. and A.P., and TRR156 (project ID 246807620) to A.P; from the German Center of Infection Research (DZIF) to S.H., B.K., H.B.-O. and A.P.; from the German Ministry of Research and Education (BMBF) Culture Challenge to A.P.; and from the European Innovative Medicines Initiate IMI (COMBACTE) to A.P.

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Eberhard Karls University Tübingen holds a patent (EP3072899B1) covering the compound lugdunin, derivatives thereof and the bacterial infection prevention by lugdunin-producing bacteria. The patent has also been filed in the USA (US2018/0155397A1). The authors declare no other competing interests.

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Heilbronner, S., Krismer, B., Brötz-Oesterhelt, H. et al. The microbiome-shaping roles of bacteriocins. Nat Rev Microbiol (2021). https://doi.org/10.1038/s41579-021-00569-w

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