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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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.
The authors declare no competing interests.
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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
Nature Chemical Biology (2022)