Aspartate aminotransferase Rv3722c governs aspartate-dependent nitrogen metabolism in Mycobacterium tuberculosis.
Robert S JansenLungelo MandyoliRyan HughesShoko WakabayashiJessica T PinkhamBruna SelbachKristine M GuinnEric J RubinJames C SacchettiniKyu Y RheePublished in: Nature communications (2020)
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, and mediates an essential but underrecognized role in metabolism: nitrogen distribution. Rv3722c deficiency leads to virulence attenuation in macrophages and mice. Our results identify aspartate biosynthesis and nitrogen distribution as potential species-selective drug targets in M. tuberculosis.
Keyphrases
- mycobacterium tuberculosis
- pulmonary tuberculosis
- binding protein
- genome wide
- escherichia coli
- pseudomonas aeruginosa
- copy number
- staphylococcus aureus
- type diabetes
- emergency department
- biofilm formation
- gene expression
- dna methylation
- cystic fibrosis
- replacement therapy
- human immunodeficiency virus
- antiretroviral therapy