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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Aspartate Aminotransferases / chemistry
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Aspartate Aminotransferases / genetics
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Aspartate Aminotransferases / metabolism*
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Aspartic Acid / metabolism*
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Bacterial Proteins / chemistry
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Bacterial Proteins / genetics
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Bacterial Proteins / metabolism*
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Cells, Cultured
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Female
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Macrophages / metabolism
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Macrophages / microbiology
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Mice
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Mice, Inbred C57BL
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Mycobacterium tuberculosis / enzymology*
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Mycobacterium tuberculosis / genetics
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Mycobacterium tuberculosis / growth & development
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Mycobacterium tuberculosis / pathogenicity
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Nitrogen / metabolism*
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Protein Binding
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Protein Conformation
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Virulence / genetics
Substances
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Bacterial Proteins
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Aspartic Acid
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Aspartate Aminotransferases
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Nitrogen