Nitrogen metabolism in mycobacteria: the key genes and targeted antimicrobials

Yufan Xu; Shiwei Ma; Zixin Huang; Longlong Wang; Sayed Haidar Abbas Raza; Zhe Wang

doi:10.3389/fmicb.2023.1149041

Nitrogen metabolism in mycobacteria: the key genes and targeted antimicrobials

Front Microbiol. 2023 May 18:14:1149041. doi: 10.3389/fmicb.2023.1149041. eCollection 2023.

Authors

Yufan Xu^#^{1

2}, Shiwei Ma^#^{1

2}, Zixin Huang^{1

2}, Longlong Wang^{1

2}, Sayed Haidar Abbas Raza³, Zhe Wang^{1

2}

Affiliations

¹ Shanghai Collaborative Innovation Center of Agri-Seeds, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China.
² Shanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China.
³ Guangdong Provincial Key Laboratory of Food Quality and Safety/Nation-Local Joint Engineering Research Center for Machining and Safety of Livestock and Poultry Products, South China Agricultural University, Guangzhou, China.

^# Contributed equally.

Abstract

Nitrogen metabolism is an important physiological process that affects the survival and virulence of Mycobacterium tuberculosis. M. tuberculosis's utilization of nitrogen in the environment and its adaptation to the harsh environment of acid and low oxygen in macrophages are closely related to nitrogen metabolism. In addition, the dormancy state and drug resistance of M. tuberculosis are closely related to nitrogen metabolism. Although nitrogen metabolism is so important, limited research was performed on nitrogen metabolism as compared with carbon metabolism. M. tuberculosis can use a variety of inorganic or organic nitrogen sources, including ammonium salts, nitrate, glutamine, asparagine, etc. In these metabolic pathways, some enzymes encoded by key genes, such as GlnA1, AnsP2, etc, play important regulatory roles in the pathogenesis of TB. Although various small molecule inhibitors and drugs have been developed for different nitrogen metabolism processes, however, long-term validation is needed before their practical application. Most importantly, with the emergence of multidrug-resistant strains, eradication, and control of M. tuberculosis will still be very challenging.

Keywords: TB; antimicrobials; drug targets; nitrogen metabolism; tuberculosis.

Publication types

Review

Grants and funding

This research was kindly supported by a grant from the National Natural Science Foundation of China (No. 32070128), National Key Research and Development Plans of China (No. 2021YFD1800401), and Shanghai Biomedical Science and Technology Support Special Project (No. 21S11900200).