Award Details:
Award Type: Catalyst
Award #: C-077
Proposal Title: A Novel Antibiotic Strategy Exploiting Metabolite Self-Toxicity
PI(s): Keith Tyo (NU) and Scott Franzblau (UIC)
Award Amount: $250,000.00
Application Cycle: Round 22 (Fall 2016)
Award Start Date: March 1, 2017
Award End Date: February 28, 2019
Abstract:
Strains of multidrug resistant Mycobacterium tuberculosis (M. tb) are appearing faster than new antibiotics, threatening a wide-spread re-emergence. This trend is true for many infectious bacteria, and the NIH has made combating antibiotic resistance a key priority. The standard drugging approach of directly inhibiting essential pathways may be exhausted. We propose a fundamentally different approach that could target a new set of non-essential M. tb proteins. Native metabolites that act as competitive inhibitors (CIs) at high levels, can be artificially raised by drug combinations. This proposal seeks to identify potentially toxic native CIs and devise strategies to increase their concentration by modulating enzymatic producers/consumers of the CI (PCI/CCI). If successful, a whole range of compounds that target non-essential enzymes (PCI/CCI) could be made antimicrobial by potentiating this self-toxicity.