title: Arginine-specific mono ADP-ribosylation in vitro of antimicrobial peptides by ADP-ribosylating toxins.
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 α- and β- defensins. Cholera toxin (CT) from Vibrio cholerae and heat labile enterotoxin (LT) from Escherichia coli both modified the human α-defensin (HNP-1) and β- 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-ribosylating toxins recognize defensins as substrates in vitro. Modifications that alter the biological activities of antimicrobial peptides may be relevant for the innate immune response. In particular, ADP-ribosylation of antimicrobial peptides may represent a novel escape mechanism adopted by pathogens to facilitate colonization of host tissues.
authors.affiliation: Novartis Vaccines & Diagnostics, Siena, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Castagnini
authors.forename: Monica
authors.initials: M
authors.lastname: Picchianti
authors.forename: Eleonora
authors.initials: E
authors.lastname: Talluri
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Biagini
authors.forename: Mariangela
authors.initials: M
authors.lastname: Del Vecchio
authors.forename: Paolo
authors.initials: P
authors.lastname: Di Procolo
authors.forename: Nathalie
authors.initials: N
authors.lastname: Norais
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Nardi-Dei
authors.forename: Enrico
authors.initials: E
authors.lastname: Balducci
mesh_terms: D036002:ADP Ribose Transferases / Q000378:metabolism; D020727:ADP-Ribosylation Factors / Q000378:metabolism*; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000378:metabolism*; D001120:Arginine / Q000378:metabolism*; D002460:Cell Line; D002772:Cholera Toxin / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009244:NAD+ Nucleosidase / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013379:Substrate Specificity; D014118:Toxins, Biological / Q000378:metabolism*; D023084:alpha-Defensins / Q000737:chemistry
chemical_list: D023181:Antimicrobial Cationic Peptides; D014118:Toxins, Biological; D023084:alpha-Defensins; C406413:human neutrophil peptide 1; D000246:Adenosine Diphosphate Ribose; D002772:Cholera Toxin; D001120:Arginine; D036002:ADP Ribose Transferases; C480854:NarE protein, Neisseria meningitidis; D009244:NAD+ Nucleosidase; D020727:ADP-Ribosylation Factors