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Toxin-antitoxin systems in bacterial growth arrest and persistence

Nature Chemical Biology volume 12, pages 208–214 (2016)Cite this article

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Abstract

Bacterial persister cells constitute a subpopulation of genetically identical, metabolically slow-growing cells that are highly tolerant of antibiotics and other environmental stresses. Recent studies have demonstrated that gene loci known as toxin-antitoxin (TA) modules play a central role in the persister state. Under normal growth conditions, antitoxins potently inhibit the activities of the toxins. In contrast, under conditions of stress, the antitoxins are selectively degraded, freeing the toxins to inhibit essential cellular processes, such as DNA replication and protein translation. This inhibition results in rapid growth arrest. In this Review, we highlight recent discoveries of these multifaceted TA systems with a focus on the newly uncovered mechanisms, especially conditional cooperativity, that are used to regulate cell growth and persistence. We also discuss the potential for targeting TA systems for antimicrobial drug discovery.

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Figure 1: Toxin-antitoxin systems.
Figure 2: TA systems in E. coli. (a) TA loci in the E. coli genome (type I systems not shown).
Figure 3: TA systems and persistence.
Figure 4: The molecular basis of conditional cooperativity.
Figure 5: Characteristics of type II TA systems that exhibit or do not exhibit conditional cooperativity.

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Acknowledgements

The authors thank all current and previous members of the Page and Peti laboratories for their contributions to this ongoing research. The Peti and Page laboratories also thank all collaborators in the toxin-antitoxin field for their critical scientific input and generous support, especially T.K. Wood (Pennsylvania State University). Grant sponsors: US National Science Foundation, grant number MCB0952550, and a Brown University Deans Award to R.P.

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  1. Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, Rhode Island, USA

    Rebecca Page

  2. Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, Rhode Island, USA

    Wolfgang Peti

  3. Department of Chemistry, Brown University, Providence, Rhode Island, USA

    Wolfgang Peti

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Page, R., Peti, W. Toxin-antitoxin systems in bacterial growth arrest and persistence. Nat Chem Biol 12, 208–214 (2016). https://doi.org/10.1038/nchembio.2044

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