DosR's multifaceted role on Mycobacterium bovis BCG revealed through multi-omics

Yingying Cui; Guanghui Dang; Hui Wang; Yiyi Tang; Mingyue Lv; Siguo Liu; Ningning Song

doi:10.3389/fcimb.2023.1292864

DosR's multifaceted role on Mycobacterium bovis BCG revealed through multi-omics

Front Cell Infect Microbiol. 2023 Nov 21:13:1292864. doi: 10.3389/fcimb.2023.1292864. eCollection 2023.

Authors

Yingying Cui¹, Guanghui Dang¹, Hui Wang¹, Yiyi Tang¹, Mingyue Lv¹, Siguo Liu¹, Ningning Song^{1

2

3}

Affiliations

¹ State Key Laboratory for Animal Disease Control and Prevention, Division of Bacterial Diseases, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
² School of Life Science and Technology, Weifang Medical University, Weifang, China.
³ Weifang Key Laboratory of Respiratory Tract Pathogens and Drug Therapy, Weifang, China.

Abstract

Mycobacterium tuberculosis (Mtb) is an intracellular bacterium that causes a highly contagious and potentially lethal tuberculosis (TB) in humans. It can maintain a dormant TB infection within the host. DosR (dormancy survival regulator) (Rv3133c) has been recognized as one of the key transcriptional proteins regulating bacterial dormancy and participating in various metabolic processes. In this study, we extensively investigate the still not well-comprehended role and mechanism of DosR in Mycobacterium bovis (M. bovis) Bacillus Calmette-Guérin (BCG) through a combined omics analysis. Our study finds that deleting DosR significantly affects the transcriptional levels of 104 genes and 179 proteins. Targeted metabolomics data for amino acids indicate that DosR knockout significantly upregulates L-Aspartic acid and serine synthesis, while downregulating seven other amino acids, including L-histidine and lysine. This suggests that DosR regulates amino acid synthesis and metabolism. Taken together, these findings provide molecular and metabolic bases for DosR effects, suggesting that DosR may be a novel regulatory target.

Keywords: DosR; Mycobacterium bovis BCG; metabonomics; proteomics; transcriptomics.

MeSH terms

BCG Vaccine
Bacterial Proteins / metabolism
Humans
Lysine / metabolism
Multiomics
Mycobacterium bovis* / genetics
Mycobacterium tuberculosis*
Tuberculosis* / microbiology

Substances

Bacterial Proteins
Lysine
BCG Vaccine

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by National Key Research and Development Program of China (2021YFD1800403), National Natural Science Foundation of China (Nos. 32273005, 32002256, 31873014).