Targeting the role of N-terminal methionine processing enzymes in Mycobacterium tuberculosis

The discovery of anti-tuberculosis agents that target new pathways is crucial for effective short-term TB therapy that will limit the development of resistance. The clinical significance of multidrug-resistant and extensively drug-resistant strains of Mycobacterium tuberculosis, latent TB and Human Immunodeficiency Virus co-infection in tuberculosis patients have made the development of new antimycobacterials more imperative. A better understanding of the major pathways that are involved in the pathogenesis, survival, and dormancy of Mtb will aid in the identification of new drug targets. Here, we review the N-terminal methionine excision (NME) pathway as a potential drug target during host infection with M. tuberculosis. The removal of the N-terminal methionine is a requirement for some proteins prior to post-translational modifications and processing. Therefore, an understanding of the physiological relevance of the two families of enzymes at the center of NME - peptide deformylases and methionine aminopeptidases - has the prospect of adding novel targets and antimycobacterials to the pipeline.