Research by: Thomas P. Wyche, René F. Ramos Alvarenga, Jeff S. Piotrowski, Megan N. Duster, Simone Warrack, Gabriel Cornilescu, Travis J. De Wolfe, Chad L. Myers, James L. Steele, John L. Markley, Tim S. Bugni
Clostridium difficile infection (CDI) has emerged as a major health threat and has been identified as a high priority by the Centers for Disease Control (CDC). Emergence of hypervirulent strains that are highly resistant and overproduce toxins has led to an increasing rate of mortality due to CDI. We discovered the antibiotic ecteinamycin from a marine Actinomadura sp. Ecteinamycin is an ionophore antibiotic that displays high potency toward C. difficile. Using both yeast and bacterial (E. coli) chemical genomics, we posit that ionophore antibiotics such as ecteinamycin hold promise as therapies for CDI due to their potency towards C. difficile and ability to block toxin action on human cells. This presentation will discuss aspects of configurational analysis including new methods using residual dipolar couplings as well as highlighting the biology underlying the promising activity of ecteinamycin.