Submitted by san2025 on December 27, 2021 - 10:27pm
Title | Aspartate aminotransferase Rv3722c governs aspartate-dependent nitrogen metabolism in Mycobacterium tuberculosis. |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | Jansen RS, Mandyoli L, Hughes R, Wakabayashi S, Pinkham JT, Selbach B, Guinn KM, Rubin EJ, Sacchettini, James C, Rhee KY |
Journal | Nat Commun |
Volume | 11 |
Issue | 1 |
Pagination | 1960 |
Date Published | 2020 04 23 |
ISSN | 2041-1723 |
Keywords | Animals, Aspartate Aminotransferases, Aspartic Acid, Bacterial Proteins, Cells, Cultured, Female, Macrophages, Mice, Mice, Inbred C57BL, Mycobacterium tuberculosis, Nitrogen, Protein Binding, Protein Conformation, Virulence |
Abstract | 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. |
DOI | 10.1038/s41467-020-15876-8 |
Alternate Journal | Nat Commun |
PubMed ID | 32327655 |
PubMed Central ID | PMC7181641 |
Grant List | U19 AI107774 / AI / NIAID NIH HHS / United States |