YjgM is a crotonyltransferase critical for polymyxin resistance of Escherichia coli

Jianpeng Zhuang; Shiqin Liu; Gao-Fei Du; Zuye Fang; Jiayi Wu; Nan Li; Tairan Zhong; Jiayi Xu; Qing-Yu He; Xuesong Sun

doi:10.1016/j.celrep.2024.114161

YjgM is a crotonyltransferase critical for polymyxin resistance of Escherichia coli

Cell Rep. 2024 Apr 27;43(5):114161. doi: 10.1016/j.celrep.2024.114161. Online ahead of print.

Authors

Jianpeng Zhuang¹, Shiqin Liu¹, Gao-Fei Du², Zuye Fang¹, Jiayi Wu¹, Nan Li¹, Tairan Zhong¹, Jiayi Xu¹, Qing-Yu He³, Xuesong Sun⁴

Affiliations

¹ MOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, China.
² MOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, China; Key Laboratory of Laboratory Diagnostics, Medical Technology School, Xuzhou Medical University, Xuzhou, Jiangsu, China.
³ MOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, China. Electronic address: tqyhe@jnu.edu.cn.
⁴ MOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, China. Electronic address: tsunxs@jnu.edu.cn.

PMID: 38678561
DOI: 10.1016/j.celrep.2024.114161

Abstract

Lysine crotonylation has attracted widespread attention in recent years. However, little is known about bacterial crotonylation, particularly crotonyltransferase and decrotonylase, and its effects on antibiotic resistance. Our study demonstrates the ubiquitous presence of crotonylation in E. coli, which promotes bacterial resistance to polymyxin. We identify the crotonyltransferase YjgM and its regulatory pathways in E. coli with a focus on crotonylation. Further studies show that YjgM upregulates the crotonylation of the substrate protein PmrA, thereby boosting PmrA's affinity for binding to the promoter of eptA, which, in turn, promotes EptA expression and confers polymyxin resistance in E. coli. Additionally, we discover that PmrA's crucial crotonylation site and functional site is Lys 164. These significant discoveries highlight the role of crotonylation in bacterial drug resistance and offer a fresh perspective on creating antibacterial compounds.

Keywords: CP: Microbiology; E. coli; YjgM; crotonylation; crotonyltransferase; polymyxin resistance.