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NAD + auxotrophy is bacteriocidal for the tubercle bacilli
Author(s) -
Vilchèze Catherine,
Weinrick Brian,
Wong KaWing,
Chen Bing,
Jacobs, Jr William R.
Publication year - 2010
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2010.07099.x
Subject(s) - auxotrophy , biology , bacilli , tubercle , microbiology and biotechnology , nad+ kinase , bacteria , biochemistry , genetics , escherichia coli , gene , enzyme
Summary The human tubercle bacillus Mycobacterium tuberculosis can synthesize NAD + using the de novo biosynthesis pathway or the salvage pathway. The salvage pathway of the bovine tubercle bacillus Mycobacterium bovis was reported defective due to a mutation in the nicotinamidase PncA. This defect prevents nicotinic acid secretion, which is the basis for the niacin test that clinically distinguishes M. bovis from M. tuberculosis . Surprisingly, we found that the NAD + de novo biosynthesis pathway ( nadABC ) can be deleted from M. bovis , demonstrating a functioning salvage pathway. M. bovis Δ nadABC fails to grow in mice, whereas M. tuberculosis Δ nadABC grows normally in mice, suggesting that M. tuberculosis can acquire nicotinamide from its host. The introduction of M. tuberculosis pncA into M. bovis Δ nadABC is sufficient to fully restore growth in a mouse, proving that the functional salvage pathway enables nicotinamide acquisition by the tubercle bacilli. This study demonstrates that NAD + starvation is a cidal event in the tubercle bacilli and confirms that enzymes common to the de novo and salvage pathways may be good drug targets.