Nicotinamide Limits Replication of Mycobacterium tuberculosis and Bacille Calmette-Guerin Within Macrophages.

ABSTRACT: Novel antimicrobials for treatment of Mycobacterium tuberculosis are needed. We hypothesized that nicotinamide (NAM) and nicotinic acid (NA) modulate macrophage function to restrict M. tuberculosis replication in addition to their direct antimicrobial properties. Both compounds had modest activity in 7H9 broth, but only NAM inhibited replication in macrophages. Surprisingly, in macrophages NAM and the related compound pyrazinamide restricted growth of bacille Calmette-Guérin but not wild-type Mycobacterium bovis, which both lack a functional nicotinamidase/pyrazinamidase (PncA) rendering each strain resistant to these drugs in broth culture. Interestingly, NAM was not active in macrophages infected with a virulent M. tuberculosis mutant encoding a deletion in pncA. We conclude that the dif

SUBMITTER: Simmons JD 

PROVIDER: S-EPMC7050990 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature