Nicotinamide Limits Replication of Mycobacterium tuberculosis and Bacille Calmette-Guérin Within Macrophages.
Animals
CHO Cells
Cricetinae
Cricetulus
Cytokines
Gene Expression Regulation
/ drug effects
Humans
Interleukin-1beta
/ genetics
Interleukin-6
/ genetics
Macrophages
/ drug effects
Microbial Sensitivity Tests
Mycobacterium bovis
/ drug effects
Mycobacterium tuberculosis
/ drug effects
Niacin
/ pharmacology
Niacinamide
/ administration & dosage
Tumor Necrosis Factor-alpha
/ genetics
U937 Cells
Vitamin B Complex
/ pharmacology
Mycobacterium tuberculosis
BCG
host-directed therapy
niacin
nicotinamide
nicotinic acid
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
02 03 2020
02 03 2020
Historique:
received:
10
04
2019
accepted:
16
10
2019
pubmed:
31
10
2019
medline:
26
11
2020
entrez:
31
10
2019
Statut:
ppublish
Résumé
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 differential activity of NAM and nicotinic acid on infected macrophages suggests host-specific NAM targets rather than PncA-dependent direct antimicrobial properties. These activities are sufficient to restrict attenuated BCG, but not virulent wild-type M. bovis or M. tuberculosis.
Identifiants
pubmed: 31665359
pii: 5610259
doi: 10.1093/infdis/jiz541
pmc: PMC7050990
doi:
Substances chimiques
Cytokines
0
Interleukin-1beta
0
Interleukin-6
0
Tumor Necrosis Factor-alpha
0
Vitamin B Complex
12001-76-2
Niacinamide
25X51I8RD4
Niacin
2679MF687A
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
989-999Subventions
Organisme : NIAID NIH HHS
ID : K08 AI143926
Pays : United States
Organisme : NIAID NIH HHS
ID : K24 AI137310
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007044
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI093646
Pays : United States
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.
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