中文版 | English
Title

Malonylome analysis uncovers the association of lysine malonylation with metabolism and acidic stress in pathogenic Mycobacterium tuberculosis

Author
Corresponding AuthorZhang,Guoliang
Publication Years
2022-12-01
DOI
Source Title
ISSN
0944-5013
EISSN
1618-0623
Volume265
Abstract
Mycobacterium tuberculosis (Mtb), the pathogenic agent of tuberculosis, remains a primary inducement of morbidity and mortality globally. Mtb have evolved mechanisms to recognize diverse signals, such as acidic pH within phagolysosomes and therefore to reprogram multiple physiological and metabolic processes to adapt to intracellular survival. Moreover, lysine malonylation has been suggested to participate in regulation of enzymes in carbon metabolism. However, lysine malonylation in Mtb and its association with acidic pH associated metabolism adaptation remain unknown. Here, we systematically characterized the comparative malonylome of Mtb H37Rv grown in normal (7H9-Tyloxapol (Ty)-7.4) and acidic (7H9-Ty-4.5) medium mimicking lysosome pH. In total, 2467 lysine malonylation sites within 1026 proteins were identified, which related to diverse biological processes, particularly accumulated in metabolic process. 1090 lysine malonylation sites from 562 proteins were quantified, among which 391 lysine malonylation sites in 273 protein were down-regulated while 40 lysine malonylation sites from 36 proteins were up-regulated in acidic medium, indicating that malonylation may participate in acidic pH associated metabolism. Accordingly, the enzyme activity of GlcB was reduced under acidic stress corresponding to decreased malonylation of GlcB compared with that of normal condition and this was further demonstrated by site-specific mutations. We further found that Mtb-CobB, a sirtuin-like deacetylase and desuccinylase, involved in demalonylase activity. Together, the Mtb malonylome not only indicates the critical role of malonylation in metabolism regulation, but may provide new insights of malonylation on metabolism adaptation to acidic micro-environment in vivo.
Keywords
URL[Source Record]
Indexed By
Language
English
SUSTech Authorship
First ; Corresponding
Funding Project
China Postdoctoral Science Foundation[2020M670085ZX];National Natural Science Foundation of China[22107045];National Natural Science Foundation of China[81802058];National Natural Science Foundation of China[81873958];National Natural Science Foundation of China[82102403];National Natural Science Foundation of China[82170009];Shenzhen Scientific and Technological Foundation[JCYJ20180228162336873];Shenzhen Scientific and Technological Foundation[KCXFZ202002011007083];Sanming Project of Medicine in Shenzhen[SZSM201911009];
WOS Research Area
Microbiology
WOS Subject
Microbiology
WOS Accession No
WOS:000863947900002
Publisher
ESI Research Field
MICROBIOLOGY
Scopus EID
2-s2.0-85138480744
Data Source
Scopus
Citation statistics
Cited Times [WOS]:1
Document TypeJournal Article
Identifierhttp://kc.sustech.edu.cn/handle/2SGJ60CL/402638
DepartmentThe Third People's Hospital of Shenzhen
Affiliation
1.National Clinical Research Center for Infectious Diseases,Guangdong Provincial Clinical Research Center for Tuberculosis,Shenzhen Third People's Hospital,Southern University of Science and Technology,Shenzhen,518112,China
2.Guangdong Centre for Tuberculosis Control,Guangzhou,510430,China
First Author AffilicationThe Third People's Hospital of Shenzhen
Corresponding Author AffilicationThe Third People's Hospital of Shenzhen
First Author's First AffilicationThe Third People's Hospital of Shenzhen
Recommended Citation
GB/T 7714
Bi,Jing,Guo,Qinglong,Zhou,Ziyuan,et al. Malonylome analysis uncovers the association of lysine malonylation with metabolism and acidic stress in pathogenic Mycobacterium tuberculosis[J]. MICROBIOLOGICAL RESEARCH,2022,265.
APA
Bi,Jing.,Guo,Qinglong.,Zhou,Ziyuan.,Huang,Xiujing.,Qin,Linxiu.,...&Zhang,Guoliang.(2022).Malonylome analysis uncovers the association of lysine malonylation with metabolism and acidic stress in pathogenic Mycobacterium tuberculosis.MICROBIOLOGICAL RESEARCH,265.
MLA
Bi,Jing,et al."Malonylome analysis uncovers the association of lysine malonylation with metabolism and acidic stress in pathogenic Mycobacterium tuberculosis".MICROBIOLOGICAL RESEARCH 265(2022).
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