arginine-specific mono adp-ribosylation in vitro of antimicrobial peptides by adp-ribosylating toxinsarginine-specific mono adp-ribosylation体外抗菌肽的adp-ribosylating毒素.pdfVIP

Arginine-Specific Mono ADP-Ribosylation In Vitro of Antimicrobial Peptides by ADP-Ribosylating Toxins 1 1,3 1 1 Marta Castagnini , Monica Picchianti , Eleonora Talluri , Massimiliano Biagini , Mariangela Del 1 1 1 1 2 Vecchio , Paolo Di Procolo , Nathalie Norais , Vincenzo Nardi-Dei , Enrico Balducci * 1 Novartis Vaccines Diagnostics, Siena, Italy, 2 School of Biosciences and Biotechnologies, University of Camerino, Camerino, Italy, 3 Department of Evolutionary Biology, University of Siena, Siena, Italy Abstract Among the several toxins used by pathogenic bacteria to target eukaryotic host cells, proteins that exert ADP-ribosylation activity represent a large and studied family of dangerous and potentially lethal toxins. These proteins alter cell physiology catalyzing the transfer of the ADP-ribose unit from NAD to cellular proteins involved in key metabolic pathways. In the present study, we tested the capability of four of these toxins, to ADP-ribosylate a- and b- defensins. Cholera toxin (CT) from Vibrio cholerae and heat labile enterotoxin (LT) from Escherichia coli both modified the human a-defensin (HNP-1) and b- defensin-1 (HBD1), as efficiently as the mammalian mono-ADP-ribosyltransferase-1. Pseudomonas aeruginosa exoenzyme S was inactive on both HNP-1 and HBD1. Neisseria meningitidis NarE poorly recognized HNP-1 as a substrate but it was completely inactive on HBD1. On the other hand, HNP-1 strongly influenced NarE inhibiting its transferase activity while enhancing auto-ADP-ribosylation. We conclude that only some arginine-specific ADP-rib