Work in the Ellermeier Lab focuses on how Gram-positive pathogens sense and respond to antibiotics and the innate immune system. Our work is primarily focused on the opportunistic human pathogen Clostridioides difficile. C. difficile is an anaerobic Gram-positive spore-forming pathogen that is the most common cause of hospital-associated diarrhea. C. difficile infections kill close to 30,000 people a year in the United States and C. difficile infections have been deemed an “urgent” threat to public health by the CDC.

Antibiotic resistance is an increasing problem in treating C. difficile infections. Our recent work has focused on understanding how C. difficile responds to antibiotics. We have identified two-component regulatory systems in C. difficile that contribute to resistance to antibiotics that target the cell envelope. C. difficile encodes >50 different two-component regulatory systems the vast majority of which have been uncharacterized.  Our data suggest that a number of these uncharacterized two-component regulatory systems are involved in regulating cell envelope biogenesis. We use a combination of genetic, molecular, biochemical, microscopy and structural approaches to dissect how these signal transduction systems function and how they induce resistance to antibiotics and the innate immune system.

The long-term goal of the lab is to understand how C. difficile senses and responds to extracellular stresses caused by antibiotics and the innate immune system and identify novel targets to treat C. difficile infections. To this end we also work with David Weiss to study C. difficile cell envelope biogenesis using a combination of genetic, biochemical and microscopy approaches to identify unique features of the C. difficile cell envelope required for growth.