Clostridioides difficile is a Gram-positive, spore-forming anaerobe and the leading cause of hospital-acquired and antibiotic-associated intestinal infections in the United States. It can cause severe diarrhea, abdominal pain, and inflammation of the colon. Our lab studies how C. difficile senses and responds to stressful conditions in the gut and the molecular strategies it uses to survive and cause disease. By uncovering these mechanisms, we aim to identify new ways to combat bacterial infections and improve patient outcomes.

Our research focuses on three main questions:

• How does C. difficile build ferrosomes, and what roles do these nanoscale iron storage compartments play during infection?
• Why does C. difficile encode so many environmental "sensors”, and how do these systems help it survive in the gut?
• How does C. difficile control its mRNA during infection, and how do specialized RNA-binding proteins support its stress responses?

It was long thought that only complex organisms like plants and animals can build internal compartments — called “organelles” — inside their cells. However, recent discoveries, including work from our lab, have revealed that bacteria can build organelles too. C. difficile, for instance, produces membrane-bound organelles called ferrosomes that safely store iron. This is a crucial ability during infection, when the host and microbes compete for iron, a nutrient essential for survival but toxic in excess. We are investigating how ferrosomes assemble, how they influence infection outcomes, and how they affect interactions among C. difficile, the gut microbiota, and the human host. These insights may reveal new therapeutic targets or inspire new nanoparticle-based drug delivery strategies.

Our work also focuses on understanding how C. difficile detects and responds to its environment. Like many bacteria, C. difficile uses two-component systems (TCSs)—molecular "sensors" that detect changes and activate stress responses. Interestingly, C. difficile has a large number of these systems, likely reflecting the wide range of hostile conditions it encounters in the gut. We are working to identify which TCSs are activated during infection, what signals they sense, and how they contribute to bacterial survival. Because TCSs are not found in human cells, they represent attractive targets for developing new antibiotics.

Additionally, we are exploring how C. difficile regulates its mRNA during infection. RNA-binding proteins (RBPs) are key players in post-transcriptional control across all domains of life, yet their roles in bacteria—particularly pathogens like C. difficile—remain poorly understood. Using a newly adapted method to systematically identify RBPs and map their interactions, we aim to uncover how these proteins contribute to C. difficile's stress adaptation and survival during infection.