Clostridium difficile-associated
diarrhea and
pseudomembranous colitis are typically treated with
vancomycin or
metronidazole, but recent increases in relapse incidence and the emergence of drug-resistant strains of C. difficile indicate the need for new
antibiotics. We previously isolated coprisin, an antibacterial
peptide from Copris tripartitus, a Korean dung beetle, and identified a nine-
amino-acid peptide in the α-helical region of it (LLCIALRKK) that had antimicrobial activity (J.-S. Hwang et al., Int. J.
Pept., 2009, doi:10.1155/2009/136284). Here, we examined whether treatment with a coprisin analogue (a
disulfide dimer of the nine
peptides) prevented
inflammation and mucosal damage in a mouse model of acute gut
inflammation established by administration of
antibiotics followed by C. difficile
infection. In this model, coprisin treatment significantly ameliorated
body weight decreases, improved the survival rate, and decreased mucosal damage and proinflammatory
cytokine production. In contrast, the coprisin analogue had no apparent
antibiotic activity against commensal bacteria, including Lactobacillus and Bifidobacterium, which are known to inhibit the colonization of C. difficile. The exposure of C. difficile to the coprisin analogue caused a marked increase in nuclear
propidium iodide (PI) staining, indicating membrane damage; the staining levels were similar to those seen with bacteria treated with a positive control for membrane disruption (
EDTA). In contrast, coprisin analogue treatment did not trigger increases in the nuclear PI staining of Bifidobacterium thermophilum. This observation suggests that the
antibiotic activity of the coprisin analogue may occur through specific membrane disruption of C. difficile. Thus, these results indicate that the coprisin analogue may prove useful as a therapeutic agent for C. difficile
infection-associated inflammatory
diarrhea and
pseudomembranous colitis.