title: Resistance of Porphyromonas gingivalis ATCC 33277 to direct killing by antimicrobial peptides is protease independent.
abstract: Antimicrobial peptides are short, positively charged, amphipathic peptides that possess a wide spectrum of antimicrobial activity and have an important role in the host's innate immunity. Lack of, or dysfunctions in, antimicrobial peptides have been correlated with infectious diseases, including periodontitis. Porphyromonas gingivalis, a gram-negative anaerobe and a major pathogen associated with periodontal diseases, is resistant to antimicrobial peptides of human and nonhuman origin, a feature that likely contributes to its virulence. Expressing a robust proteolytic activity, P. gingivalis hydrolyzes antimicrobial peptides. In this study, P. gingivalis inactivated three antimicrobial peptides, while a d-enantiomer was resistant to degradation. P. gingivalis was resistant to the protease-resistant d-enantiomer peptide, and importantly, a protease-deficient P. gingivalis mutant was also resistant to the antimicrobial peptide. Finally, the binding of a fluorescently labeled antimicrobial peptide to protease-deficient P. gingivalis was much weaker than the binding of susceptible Escherichia coli. Our results suggest that the resistance of P. gingivalis ATCC 33277 to direct killing by antimicrobial peptides is protease independent and results (at least partially) from the low affinity of antimicrobial peptides to P. gingivalis.
authors: Institute of Dental Sciences, The Hebrew University-Hadassah School of Dental Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel. giladba@ekmd.huji.ac.il
authors: Gilad
authors: G
authors: Bachrach
authors: Hamutal
authors: H
authors: Altman
authors: Paul E
authors: PE
authors: Kolenbrander
authors: Natalia I
authors: NI
authors: Chalmers
authors: Michal
authors: M
authors: Gabai-Gutner
authors: Amram
authors: A
authors: Mor
authors: Michael
authors: M
authors: Friedman
authors: Doron
authors: D
authors: Steinberg
mesh_terms: D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D054808:Histatins / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism*; D016966:Porphyromonas gingivalis / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D054808:Histatins; C494062:dhvar4 peptide; D010447:Peptide Hydrolases; D054804:Cathelicidins