The role of methionine in tuberculosis and its potential clinical significance

Abstract

Tuberculosis (TB) remains a significant global health challenge. Multidrug-resistant tuberculosis (MDR-TB) holds a substantial health risk, and only a limited number of patients receive treatment for drug-resistant tuberculosis. Various studies have been conducted to address this condition, including through metabolic approaches to further understand the mechanisms of tuberculosis infection, one of which is methionine. There are various enzymes in the Mycobacterium tuberculosis (MTB) methionine biosynthesis pathway, the key enzymes such as MetX, MetC, MetE/MetH, MetK, MTHFR, and BCAT are essential in the biosynthesis of methionine, and hindering these enzyme activities may hold potential for new antitubercular drug development. Deletion of the metA gene weakens MTB, making it more prone to host immune responses. There is also the role of cobalamin, where cobalamin availability regulates the choice between metE and metH in methionine biosynthesis. Methionine plays a crucial role in bacterial protein translation and antioxidant activities. In bacteria including MTB, the initial methionine is formulated; this process involves several enzymes such as FMT, MetRS, PDF, and MetAP. Some compounds targeting MetAP have been identified to have significant inhibitory action against MTB, such as transitmycin and bengamides, and this also includes the drug resistant strain. Methionine supplementation alongside vitamin B-complex have shown to improve drug-induced toxicity in tuberculosis patients, this due to methionine serves as precursor to antioxidant glutathione. Metabolomics studies have shown that altered methionine levels in tuberculosis infection, with samples taken from human blood or urine show significantly lower levels in patients with active TB or failed treatment groups. This review aims to discuss the role of methionine in Mycobacterium tuberculosis and the progress of research targeting methionine metabolism and function.