Targeting endogenous gaseous signaling molecules as novel host-directed therapies against tuberculosis infection

Abstract

Tuberculosis (TB) is a chronic pulmonary disease caused by Mycobacterium tuberculosis which is a major cause of morbidity and mortality worldwide. Due to the complexity of disease and its continuous global spread, there is an urgent need to improvise the strategies for prevention, diagnosis, and treatment. The current anti-TB regimen lasts for months and warrants strict compliance to clear infection and to minimize the risk of development of multi drug-resistant tuberculosis. This underscores the need to have new and improved therapeutics for TB treatment. Several studies have highlighted the unique ability of Mycobacterium tuberculosis to exploit host factors to support its survival inside the intracellular environment. One of the key players to mycobacterial disease susceptibility and infection are endogenous gases such as oxygen, nitric oxide, carbon monoxide and hydrogen sulfide. Nitric oxide and carbon monoxide as the physiological gaseous messengers are considered important to the outcome of Mycobacterium tuberculosis infection. The role of hydrogen sulfide in human tuberculosis is yet not fully elucidated, but this gas has been shown to play a significant role in bacterial respiration, growth and pathogenesis. This review will focus on the host factors majorly endogenous gaseous signaling molecules which contributes to Mycobacterium tuberculosis survival inside the intracellular environment and highlight the potential therapeutic targets.

Keywords:

• Mycobacterium tuberculosis
• drug-resistance
• host-factors
• carbon-monoxide
• nitric-oxide
• hydrogen sulfide
• therapeutic-targets

Disclosure statement

The authors report no conflict of interest.

Additional information

Funding

The research in the Laboratory of Infection Biology and Translational Research is supported by AIIMS Intramural grant (A-638), HarGobind Khorana Innovative Young Biotechnologist Award [BT/11/IYBA/2018/01], DST-SERB [CRG/2018/004510], Life Science Research Board (LSRB), DRDO, India [LSRB-375/SH&DD/2020] [VS]. Ms. Sheetal Negi acknowledges support from CSIR, India for a Junior Research fellowship.