Selective arginines are important for the antibacterial activity and host cell interaction of human alpha-defensin 5

Defensins constitute a major family of natural Antimicrobial Peptides that protect the host against microbial invasion. Here, we report on the Antibacterial properties and cellular interaction of Human Defensin 5 as a function of its positive charge and hydrophobicity. We find that selective replacement of arginine residues in HD-5 by alanine or charge-neutral lysine residues reduces Antibacterial killing as well as host cell interaction. We identify arginines at positions 9 and 28 in the HD-5 sequence as particularly important for its function. Replacement of arginine at position 13 to Histidine, as observed in a Crohn's disease patient, reduced Bacterial killing strain-selectively. Finally, we find that HD-5 interacts with host cells via receptor-mediated mechanisms.