Systematic analysis of lysine crotonylation in human macrophages responding to MRSA infection

Hao Zhang; Wei Ma; Haoru Liu; Wanqi Tang; Junjie Shu; Jianping Zhou; Hongsheng Zheng; Hongyan Xiao; Xue Yang; Daoyan Liu; Huaping Liang; Xia Yang

doi:10.3389/fcimb.2023.1126350

Systematic analysis of lysine crotonylation in human macrophages responding to MRSA infection

Front Cell Infect Microbiol. 2023 Feb 8:13:1126350. doi: 10.3389/fcimb.2023.1126350. eCollection 2023.

Authors

Hao Zhang^{1

2}, Wei Ma¹, Haoru Liu¹, Wanqi Tang¹, Junjie Shu¹, Jianping Zhou³, Hongsheng Zheng¹, Hongyan Xiao¹, Xue Yang¹, Daoyan Liu¹, Huaping Liang¹, Xia Yang¹

Affiliations

¹ Department of Wound Infection and Drug, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China.
² Deparment of Critical Care Medicine, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China.
³ College of Basic Medical Sciences, Panzihua University, Panzihua, China.

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most commonly encountered bacteria found in healthcare clinics and has been ranked a priority 2 pathogen. Research is urgently needed to develop new therapeutic approaches to combat the pathogen. Variations in the pattern of protein posttranslational modifications (PTMs) of host cells affect physiological and pathological events, as well as therapeutic effectiveness. However, the role of crotonylation in MRSA-infected THP1 cells remains unknown. In this study, we found that crotonylation profiles of THP1 cells were altered after MRSA infection. It was then confirmed that lysine crotonylation profiles of THP1 cells and bacteria were different; MRSA infection inhibited global lysine crotonylation (Kcro) modification but partially elevated Kcro of host proteins. We obtained a proteome-wide crotonylation profile of THP1 cells infected by MRSA further treated by vancomycin, leading to the identification of 899 proteins, 1384 sites of which were down-regulated, and 160 proteins with 193 sites up-regulated. The crotonylated down-regulated proteins were mainly located in cytoplasm and were enriched in spliceosome, RNA degradation, protein posttranslational modification, and metabolism. However, the crotonylated up-regulated proteins were mainly located in nucleus and significantly involved in nuclear body, chromosome, ribonucleoprotein complex, and RNA processing. The domains of these proteins were significantly enriched on RNA recognition motif, and linker histone H1 and H5 families. Some proteins related to protecting against bacterial infection were also found to be targets of crotonylation. The present findings point to a comprehensive understanding of the biological functions of lysine crotonylation in human macrophages, thereby providing a certain research basis for the mechanism and targeted therapy on the immune response of host cells against MRSA infection.

Keywords: crotonylated modification; host cells; multi-drug-resistant bacteria; proteome; response.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Humans
Lysine / metabolism
Methicillin-Resistant Staphylococcus aureus*
Protein Processing, Post-Translational

Substances

Lysine

Grants and funding

The project is supported by the Natural Science Foundation of Chongqing (No. cstc2020jcyj- msxmX0497) and special Fund of China (No. 2021-JCJQ-JJ-1081).