Cryptdins: endogenous antibiotic peptides of small intestinal Paneth cells.

We purified three peptides ("cryptdins") from the small intestines of mice, established their primary amino acid sequences and examined their antimicrobial activity. Their primary sequences revealed approximately 50% identity to a group of antimicrobial defensins that we had previously isolated from the granules of rat neutrophils. In addition to their ability to kill Gram-positive (L. monocytogenes) and Gram-negative bacteria (E. coli and S. typhimurium) in vitro, the peptides were much more active against an avirulent (phoP) S. typhimurium strain than against its isogenic, mouse-virulent progenitor. Overall, these data suggest that endogenous antimicrobial peptides produced by Paneth cells may protect small intestinal crypts, which are critical sites of epithelial cell renewal, from invasion by autochthonous flora or by perorally acquired potential pathogens, such as Listeria and Salmonella.