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

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 po...

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Autores principales: Zhang, Hao, Ma, Wei, Liu, Haoru, Tang, Wanqi, Shu, Junjie, Zhou, Jianping, Zheng, Hongsheng, Xiao, Hongyan, Yang, Xue, Liu, Daoyan, Liang, Huaping, Yang, Xia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9945341/
https://www.ncbi.nlm.nih.gov/pubmed/36844408
http://dx.doi.org/10.3389/fcimb.2023.1126350
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author Zhang, Hao
Ma, Wei
Liu, Haoru
Tang, Wanqi
Shu, Junjie
Zhou, Jianping
Zheng, Hongsheng
Xiao, Hongyan
Yang, Xue
Liu, Daoyan
Liang, Huaping
Yang, Xia
author_facet Zhang, Hao
Ma, Wei
Liu, Haoru
Tang, Wanqi
Shu, Junjie
Zhou, Jianping
Zheng, Hongsheng
Xiao, Hongyan
Yang, Xue
Liu, Daoyan
Liang, Huaping
Yang, Xia
author_sort Zhang, Hao
collection PubMed
description 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.
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spelling pubmed-99453412023-02-23 Systematic analysis of lysine crotonylation in human macrophages responding to MRSA infection Zhang, Hao Ma, Wei Liu, Haoru Tang, Wanqi Shu, Junjie Zhou, Jianping Zheng, Hongsheng Xiao, Hongyan Yang, Xue Liu, Daoyan Liang, Huaping Yang, Xia Front Cell Infect Microbiol Cellular and Infection Microbiology 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. Frontiers Media S.A. 2023-02-08 /pmc/articles/PMC9945341/ /pubmed/36844408 http://dx.doi.org/10.3389/fcimb.2023.1126350 Text en Copyright © 2023 Zhang, Ma, Liu, Tang, Shu, Zhou, Zheng, Xiao, Yang, Liu, Liang and Yang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Zhang, Hao
Ma, Wei
Liu, Haoru
Tang, Wanqi
Shu, Junjie
Zhou, Jianping
Zheng, Hongsheng
Xiao, Hongyan
Yang, Xue
Liu, Daoyan
Liang, Huaping
Yang, Xia
Systematic analysis of lysine crotonylation in human macrophages responding to MRSA infection
title Systematic analysis of lysine crotonylation in human macrophages responding to MRSA infection
title_full Systematic analysis of lysine crotonylation in human macrophages responding to MRSA infection
title_fullStr Systematic analysis of lysine crotonylation in human macrophages responding to MRSA infection
title_full_unstemmed Systematic analysis of lysine crotonylation in human macrophages responding to MRSA infection
title_short Systematic analysis of lysine crotonylation in human macrophages responding to MRSA infection
title_sort systematic analysis of lysine crotonylation in human macrophages responding to mrsa infection
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9945341/
https://www.ncbi.nlm.nih.gov/pubmed/36844408
http://dx.doi.org/10.3389/fcimb.2023.1126350
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