Juan D. Unciti-Broceta,Institute Investigacion Biosanitaria Of Granada Ibig |
Jose MacEira,Institute Investigacion Biosanitaria Of Granada Ibig |
Sonia Morales,Institute Investigacion Biosanitaria Of Granada Ibig |
Angelica Garcia-Perez,Institute Investigacion Biosanitaria Of Granada Ibig |
And 2 more authors.
Journal of Biological Chemistry | Year: 2013
Background: Nicotinamide is a soluble compound of the vitamin B3 group with antimicrobial activity. Results: Nicotinamide causes disruption of the lysosome and inhibits the cathepsin b-like enzyme, an essential lysosomal protease in trypanosomatids. Conclusion: Nicotinamide kills African trypanosomes by targeting the cathepsin b-like protease. Significance: These results demonstrate for the first time the inhibitory effect of nicotinamide on a protease. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.
PubMed | Institute Investigacion Biosanitaria Of Granada Ibig
Type: Journal Article | Journal: The Journal of biological chemistry | Year: 2013
Nicotinamide, a soluble compound of the vitamin B3 group, has antimicrobial activity against several microorganisms ranging from viruses to parasite protozoans. However, the mode of action of this antimicrobial activity is unknown. Here, we investigate the trypanocidal activity of nicotinamide on Trypanosoma brucei, the causative agent of African trypanosomiasis. Incubation of trypanosomes with nicotinamide causes deleterious defects in endocytic traffic, disruption of the lysosome, failure of cytokinesis, and, ultimately, cell death. At the same concentrations there was no effect on a cultured mammalian cell line. The effects on endocytosis and vesicle traffic were visible within 3 h and can be attributed to inhibition of lysosomal cathepsin b-like protease activity. The inhibitory effect of nicotinamide was confirmed by a direct activity assay of recombinant cathepsin b-like protein. Taken together, these data demonstrate that inhibition of the lysosomal protease cathepsin b-like blocks endocytosis, causing cell death. In addition, these results demonstrate for the first time the inhibitory effect of nicotinamide on a protease.