Taking the Sting out of Tunicamycin: A Novel Approach Significantly Reduces the Cytotoxicity of this Nucleoside Antibiotic

Cochrane, S. (Presenter)

Activity: Talk or presentation typesInvited talk

Description

Antibiotic resistance constitutes one of the most significant challenges to human health, with the continued emergence of multidrug resistant bacteria decreasing the efficacy of existing antibiotics. A worst-case scenario was realized last year when a patient in the USA died from an infection caused by a strain of Enterobacteriaceae that was resistant to all available antibiotics.1 Thus, there is an urgent need for new antibiotics. Tunicamycin is a nucleoside antibiotic that inhibits peptidoglycan biosynthesis by binding to the UDP-MurNAc-pentapeptide phosphotransferase MraY.2 However, tunicamycin also binds to dolichyl-phosphate-GlcNAc-phosphotransferase in eukaryotes, which is the first committed step in post-translational glycosylation.3 This results in significant cytotoxicity and therefore removes the utility of tunicamycin as an antibiotic. Our lab has developed new tunicamycin analogues with potent activity against Mycobacterium tuberculosis that display very low cytoxicity.
Period20 Jun 2017
Event title25th American Peptide Symposium
Event typeConference
LocationWhistler, Canada