Nicotinamide or vitamin B3 is commonly used as an immunomodulatory agent in treatment of a number of human diseases. We have recently shown that nicotinamide has potent antimicrobial activity against Staphylococcus aureus and stimulates host killing of the pathogen through activation of transcription regulator CEBP epsilon and its downstream antimicrobial effectors. Nicotinamide is effective when administered prior or after S. aureus infection, and in preliminary experiments, nicotinamide also shows significant activity against select against Gram-negative pathogens such as Klebsiella and Pseudomonas. Based on these findings, we propose to investigate the efficacy of nicotinamide as an immune boosting agent against a broader range of pathogens, including Gram-positive and Gram-negative bacteria with significant antibiotic-resistance profile. We will investigate and optimize nicotinamide treatment strategies to inform on the designs of future clinical trials.

Public Health Relevance

We recently discovered that Nicotinamide (vitamin B3) has potent immunostimulatory activity that protects the host against infection by Staphylococcus aureus, including MRSA. In the current proposal, we seek to determine whether nicotinamide has broad antimicrobial activity against other human pathogens, including antibiotic-resistant pathogens. We will also investigate and optimize nicotinamide treatment strategies to facilitate design of future clinical trials.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI112812-01
Application #
8752702
Study Section
Drug Discovery and Mechanisms of Antimicrobial Resistance Study Section (DDR)
Program Officer
Huntley, Clayton C
Project Start
2014-07-04
Project End
2016-06-30
Budget Start
2014-07-04
Budget End
2015-06-30
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Cedars-Sinai Medical Center
Department
Type
DUNS #
City
Los Angeles
State
CA
Country
United States
Zip Code
90048