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Bacterial virulence mediated by orthogonal post-translational modification

Nature Chemical Biology volume 16, pages 1043–1051 (2020)Cite this article

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Abstract

Many bacterial pathogens secrete virulence factors, also known as effector proteins, directly into host cells. These effectors suppress pro-inflammatory host signaling while promoting bacterial infection. A particularly interesting subset of effectors post-translationally modify host proteins using novel chemistry that is not otherwise found in the mammalian proteome, which we refer to as ‘orthogonal post-translational modification’ (oPTM). In this Review, we profile oPTM chemistry for effectors that catalyze serine/threonine acetylation, phosphate β-elimination, phosphoribosyl-linked ubiquitination, glutamine deamidation, phosphocholination, cysteine methylation, arginine N-acetylglucosaminylation, and glutamine ADP-ribosylation on host proteins. AMPylation, a PTM that could be considered orthogonal until only recently, is also discussed. We further highlight known cellular targets of oPTMs and their resulting biological consequences. Developing a complete understanding of oPTMs and the host cell processes they hijack will illuminate critical steps in the infection process, which can be harnessed for a variety of therapeutic, diagnostic, and synthetic applications.

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Fig. 1: Secreted bacterial effectors wage a biochemical war in host cells.
Fig. 2: A subset of bacterial effectors catalyze orthogonal post-translational modifications (oPTMs) in host cells.
Fig. 3: Bacterial effectors use oPTMs to silence pro-inflammatory signaling through the MAPK and NFκB pathways.
Fig. 4: Bacterial effectors use oPTMs to interfere with the host ubiquitin-proteasome system.
Fig. 5: Bacterial effectors use oPTMs to alter host GTPase activity.

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Acknowledgements

This work was supported in part by a Tufts Collaborates Award to R.A.S. The authors gratefully acknowledge K. Allen, D. Walt, and J. Kritzer for helpful feedback regarding the preparation of this manuscript.

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    Kaitlin A. Chambers & Rebecca A. Scheck

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Chambers, K.A., Scheck, R.A. Bacterial virulence mediated by orthogonal post-translational modification. Nat Chem Biol 16, 1043–1051 (2020). https://doi.org/10.1038/s41589-020-0638-2

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