Resistance of Porphyromonas gingivalis ATCC 33277 to direct killing by antimicrobial peptides is protease independent.
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.
Bachrach
Gilad
G
Institute of Dental Sciences, The Hebrew University-Hadassah School of Dental Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel. giladba@ekmd.huji.ac.il
Altman
Hamutal
H
Kolenbrander
Paul E
PE
Chalmers
Natalia I
NI
Gabai-Gutner
Michal
M
Mor
Amram
A
Friedman
Michael
M
Steinberg
Doron
D
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
D023181:Antimicrobial Cationic Peptides; D054808:Histatins; C494062:dhvar4 peptide; D010447:Peptide Hydrolases; D054804:Cathelicidins