title: Gingipains produced by Porphyromonas gingivalis ATCC49417 degrade human-β-defensin 3 and affect peptide's antibacterial activity in vitro.
abstract: Porphyromonas gingivalis, one of the major pathogen associated with periodontitis, is a highly proteolytic bacterial species. Production of proteases is a common microbial virulence factor that enables the destruction of host tissues and evasion from host defense mechanisms. Antimicrobial peptides are important effector molecules of the innate immune system with a broad range of antimicrobial and immunoregulatory activities. We and others have previously demonstrated that P. gingivalis is relatively resistant to the bactericidal activity of the human β-defensin 3 (hBD3). In this study, ability of proteases released by the pathogenic strain of P. gingivalis ATCC 49417 to degrade hBD3 and to affect the antibacterial properties of the peptide was assessed. P. gingivalis culture supernatants (CS) were found to degrade hBD3 in a concentration- and time-dependent manner. Such degradation was mainly due to the activity of Arg and Lys-gingipains, as pretreatment of CS with inhibitors selective for this class of proteases abolished CS ability to degrade hBD3. Importantly, preincubation of hBD3 with CS reduced peptide's antibacterial activity against a susceptible strain of Staphylococcus aureus, while the presence of gingipain inhibitors in the bactericidal assay increased P. gingivalis susceptibility to hBD3. Altogether these results suggest that gingipains may have a role in the resistance of P. gingivalis ATCC 49417 to hBD3.
authors.affiliation: Dipartimento di Patologia Sperimentale, Biotecnologie Mediche, Infettivologia ed Epidemiologia, University of Pisa, Pisa, Italy.
authors.forename: Giuseppantonio
authors.initials: G
authors.lastname: Maisetta
authors.forename: Franca Lisa
authors.initials: FL
authors.lastname: Brancatisano
authors.forename: Semih
authors.initials: S
authors.lastname: Esin
authors.forename: Mario
authors.initials: M
authors.lastname: Campa
authors.forename: Giovanna
authors.initials: G
authors.lastname: Batoni
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D000080867:Gingipain Cysteine Endopeptidases; D006801:Humans; D016966:Porphyromonas gingivalis / Q000201:enzymology*; D013211:Staphylococcus aureus / Q000187:drug effects; D023083:beta-Defensins / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: D018829:Adhesins, Bacterial; D000900:Anti-Bacterial Agents; C422950:DEFB103A protein, human; D000080867:Gingipain Cysteine Endopeptidases; D023083:beta-Defensins; D003546:Cysteine Endopeptidases