"We think that this toxin makes disease more severe by killing beneficial eosinophils, which seem to play an important role in promoting a healthy immune response during C. difficile infection. When the eosinophils were depleted with an antibody or by the toxin, we saw dramatically increased inflammation. Restoring eosinophils by transferring them from a mouse that cannot recognize the toxin prevented the damage inflicted by the epidemic strain," explained Cowardin, who is now a postdoctoral fellow at Washington University in St. Louis.
"This builds on previous work in our lab showing that eosinophils are beneficial and suggests that one reason this strain causes such severe disease is due to its ability to kill these cells."
Cowardin also uncovered the mechanism of action of the toxin. Apparently the toxin takes advantage of a specific human protein that can recognize bacteria; the protein is a critical part of the immune response. Thus, C. difficile gets around the natural defenses of the body. Revealing the mode of action of the toxin opens up the possibility of developing therapeutics to block it, and blocking the action of the toxin rescues the damage done to gut cells.
"Nearly every day that I care for patients I am faced with this potentially deadly infection," noted Petri. "Carrie Cowardin's discovery of why this strain of C. diff is so dangerous, and most importantly how to combat it, is a huge and most needed advance."
Sources: CDC, Phys.org via UVA, Medscape, Nature Microbiology