Gene rv3722c of Mycobacterium tuberculosis is essential for in vitro growth, and encodes a putative pyridoxal phosphate-binding protein of unknown function. Here we use metabolomic, genetic and structural approaches to show that Rv3722c is the primary aspartate aminotransferase of M. tuberculosis...
Mycobacterium tuberculosis is a global killer causing over a million deaths from tuberculosis (TB) every year. It is therefore a major burden on human health. To reduce the deadly impact of TB, we need a better understanding of the strategies used by M. tuberculosis to adapt its...
The evolution of new enzymatic functions is constrained and guided by the architecture of an organism’s metabolic and regulatory networks and environmental constraints. Here, we identify a kinase that has evolved from pyruvate phosphate dikinase. Through biochemical and systems-lev...
Mycobacterium tuberculosis (Mtb), the cause of tuberculosis, kills over one million people worldwide each year. Mtb is classified into ten distinct lineages, each harboring unique genetic changes that influence its survival, virulence, and transmissibility. Although metabolism plays a cr...
Tuberculosis remains the leading cause of death from a single infectious agent worldwide, and the growing prevalence of multi-drug resistant Mycobacterium tuberculosis (Mtb) underscores the urgent need for antibiotics with novel mechanisms of action. Here, we characterize BVL3572S, a hydroxamic a...
Mycobacterium tuberculosis (Mtb) survives host defences by adapting to host conditions, including acid stress, during infection. A critical survival strategy involves pH homeostasis, mediated by complex signalling systems that regulate metabolic reprogramming and stress responses. While ...
The human pathogen Mycobacterium tuberculosis (Mtb) devotes a significant fraction of its genome to fatty acid metabolism. Although Mtb depends on host fatty acids as a carbon source, fatty acid b-oxidation is mediated by genetically redundant enzymes, which has hampered the development of antitu...
Tuberculosis (TB) remains a global health threat, aggravated by the emergence of drug-resistant strains. This study aims to identify genes and metabolic pathways with increased vulnerability in drug-resistant Mycobacterium tuberculosis strains compared to their drug-susceptible counterparts. Usin...