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

Bi，Jing1; Guo，Qinglong1; Zhou，Ziyuan1; Huang，Xiujing1; Qin，Linxiu1; Tao，Xiaoyu1; Ye，Taosheng1; Chen，Liang2; Li，Guobao1; Wang，Zhaoqin1; Liu，Lei1; Zhang，Guoliang1

2022-12-01

10.1016/j.micres.2022.127209

MICROBIOLOGICAL RESEARCH   Impact Factor & Quartile

0944-5013

1618-0623

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.

Acidic pH Lysine malonylation Malonylome Mycobacterium tuberculosis (Mtb) Post-translational modification

SCI

English

First ; Corresponding

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];

Microbiology

Microbiology

WOS:000863947900002

ELSEVIER GMBH

MICROBIOLOGY

2-s2.0-85138480744

Scopus

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

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.

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.

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).