01977nas a2200217   4500000000100000008004100001260002500042100001200067700001200079700001400091700001300105700001100118700001100129700001200140700001500152245012500167856017300292490000600465520127400471022001401745       2022                            d  bMicrobiology Society1 aBorah K1 aBeyß M1 aGirardi K1 aMendum T1 aLara F1 aNöh K1 aBeste D1 aMcFadden J00aProbing mycobacterial metabolism in tuberculosis and leprosy to identify vulnerable metabolic nodes for drug development  uhttps://www.microbiologyresearch.org/docserver/fulltext/acmi/4/5/acmi.ac2021.po0271.pdf?expires=1653987460&id=id&accname=guest&checksum=FB4F1AFAA9CE148FDB3117BA3ECDF5430 v43 a<p>Metabolism of pathogens in infectious diseases is important for their survival, virulence and pathogenesis. Mycobacterial pathogens successfully scavenge multiple host nutrient sources in the intracellular niche. It is therefore important to identify the intracellular nutrient sources and their metabolic fates in these pathogens. Metabolic phenotype of an organism is defined by metabolic fluxes. We quantified in vivo fluxes of the pathogens and probed host-bacterial metabolic cross talks in tuberculosis (TB) and leprosy using systems-based strategies and techniques of isotopic labelling, metabolic modelling and metabolic flux analysis (MFA). We show that the TB pathogen metabolizes a number of carbon and nitrogen sources in human macrophages and identified vulnerable nodes such as glutamine and serine biosynthesis as potential drug targets. Mycobacterium leprae, the leprosy causing pathogen, uses host cell glucose in infected schwann cells and the enzyme, phoenolpyruvate carboxylase is a potential drug target. Our research provides an understanding of the intracellular diets and metabolism of these important human pathogens and identified vulnerable metabolic nodes that can be used for developing innovative chemotherapies in TB and leprosy.</p>
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