Clostridioides difficile Biofilm and Spore Production in Response to Antibiotic and Immune Stress
Antimicrobial Peptides the best alternative to Antibiotics
Clostridioides (Clostridium) difficile, an anaerobic, spore-forming Gram-positive pathogenic bacterium, is a major cause of hospital-acquired infections and can persist as surface-attached biofilms for protection from antibiotic and immune stress. C. difficile can form biofilms as a single species or with other anaerobic intestinal bacteria. The environmental signals that cause individual cells to secrete toxins, form biofilms, or develop into spores that can spread the infection to new patients are unknown. In these studies, we investigate bacterial responses to different stress. Antimicrobial host-defense peptides (HDPs) produced by animal immune systems are promising candidates to develop novel therapies for bacterial infection because they cause oxidative stress that damages multiple targets in bacterial cells, so it is difficult for bacteria to evolve resistance to these attacks. We investigate antibiotic treatments, metal ions and sugars, and antimicrobial peptide treatments to determine how C. difficile reacts to multiple environmental stresses like those from antibiotic treatment or the human immune system. In our investigation of C. difficile and HDPs in an anaerobic environment, we found that the interaction of piscidin and copper is different in different oxygen environments. Antibiotics and oxidative stresses from other sources cause the cells to form spores and/or biofilms to protect themselves, but Piscidins kill vegetative C. difficile cells without triggering these protective responses. Piscidins are highly active against C. difficile and could be a good candidate for drug development.