Antimicrobial Discovery
To effectively address antibiotic resistance, we need to discover new antibiotics and antimicrobial strategies. Our group is approaching this in several ways with an emphasis of using Chemical Biology and Chemical Genetics strategies and in particular emphasizing microbial natural products as sources of new bioactive chemical matter. We are focused on bacterial, fungal and malarial parasite pathogens to this end.
Antibiotic Adjuvants
Compounds that improve the activity of antibiotics for example increasing potency, blocking resistance, etc. are termed antibiotic adjuvants. We are screening synthetic and natural product compounds for their ability potentiate antibiotics in a number of assays including direct inhibition of known resistance mechanisms, increasing activity of antibiotics against Gram negative bacteria among others.
Selected Publications
Novel therapeutic leads
Antibiotics that kill a broad spectrum of bacteria are not the only strategy to treat infection. Reducing the virulence of pathogens, improving the reactivity of the host innate immune response, and the discovery of highly narrow spectrum antimicrobials are others. Here we are screening natural products in particular and combinations of agents for these desired phenotypes.
Selected Publications
Synthetic Biology to increase antimicrobial chemical diversity
Natural products are proven to be excellent leads for new antibiotics and other therapeutics. They represent privileged chemical matter with intrinsic bioactivity. Exploring and expanding this chemical matter is readily amenable to synthetic biology strategies. We are exploring antimicrobial natural product biosynthetic mechanism and endeavoring to use tailoring enzymes to expand the chemical diversity of several scaffolds.
Selected Publications
A Focus on Microbial Natural Products: The WAC Library
Living organisms have proven to be the most reliable source of bioactive chemicals with antimicrobial activity. Environmental microbes continue to be outstanding resources for the identification of new chemical scaffolds that perturb microbial biology. We are searching for new bioactive agents derived from these sources as starting points for new antimicrobial agents and to facilitate this we have established the Wright Actinomycete Collection (WAC). This library includes approximately 10,000 strains collected from a myriad of environments and includes over 25 distinct genera.