Issue 17, 2021

Chemoproteomic profiling of itaconations in Salmonella

Abstract

Itaconate is an immunoregulatory and anti-bacterial metabolite, and plays important roles in host–pathogen interactions. Chemoproteomic strategies have been used to explore the anti-inflammatory effects of itaconate on activated macrophages and it has been found that many key proteins in immune pathways were modified; however, how itaconate modulates pathogens was not fully understood. Here, we have designed and synthesized a series of itaconate-based bioorthogonal probes, which enable quantitative and site-specific profiling of itaconated proteins and sites in Salmonella. Among many proteins related to energy metabolism, we identified a key enzyme involved in the glyoxylate cycle, isocitrate lyase (ICL), as the most prominent target. Covalent modification of the active-site cysteine in ICL by itaconate abolishes the enzyme activity and suppresses bacterial growth. Our chemoproteomic study has uncovered the wide array of itaconation targets in Salmonella and provided a comprehensive resource for understanding the anti-bacterial function of this intriguing metabolite.

Graphical abstract: Chemoproteomic profiling of itaconations in Salmonella

Supplementary files

Article information

Article type
Edge Article
Submitted
03 feb. 2021
Accepted
05 mar. 2021
First published
31 mar. 2021
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2021,12, 6059-6063

Chemoproteomic profiling of itaconations in Salmonella

Y. Zhang, W. Qin, D. Liu, Y. Liu and C. Wang, Chem. Sci., 2021, 12, 6059 DOI: 10.1039/D1SC00660F

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