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 Febr. 2021
Accepted
05 Marts 2021
First published
31 Marts 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

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party commercial publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements