Peptide-Based Inhibitors of Fimbrial Biogenesis in Porphyromonas gingivalis.

Autor:	Alaei SR; Department of Molecular Genetics and Microbiology, School of Medicine, Stony Brook University, Stony Brook, New York, USA.; Center for Infectious Diseases, Stony Brook University, Stony Brook, New York, USA., Park JH; Department of Molecular Genetics and Microbiology, School of Medicine, Stony Brook University, Stony Brook, New York, USA.; Center for Infectious Diseases, Stony Brook University, Stony Brook, New York, USA., Walker SG; Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, New York, USA., Thanassi DG; Department of Molecular Genetics and Microbiology, School of Medicine, Stony Brook University, Stony Brook, New York, USA david.thanassi@stonybrook.edu.; Center for Infectious Diseases, Stony Brook University, Stony Brook, New York, USA.
Jazyk:	angličtina
Zdroj:	Infection and immunity [Infect Immun] 2019 Feb 21; Vol. 87 (3). Date of Electronic Publication: 2019 Feb 21 (Print Publication: 2019).
DOI:	10.1128/IAI.00750-18
Abstrakt:	Periodontitis is a progressive inflammatory disease that affects roughly half of American adults. Colonization of the oral cavity by the Gram-negative bacterial pathogen Porphyromonas gingivalis is a key event in the initiation and development of periodontal disease. Adhesive surface structures termed fimbriae (pili) mediate interactions of P. gingivalis with other bacteria and with host cells throughout the course of disease. The P. gingivalis fimbriae are assembled via a novel mechanism that involves proteolytic processing of lipidated precursor subunits and their subsequent polymerization on the bacterial surface. Given their extracellular assembly mechanism and central roles in pathogenesis, the P. gingivalis fimbriae are attractive targets for anti-infective therapeutics to prevent or treat periodontal disease. Here we confirm that conserved sequences in the N and C termini of the Mfa1 fimbrial subunit protein perform critical roles in subunit polymerization. We show that treatment of P. gingivalis with peptides corresponding to the conserved C-terminal region inhibits the extracellular assembly of Mfa fimbriae on the bacterial surface. We also show that peptide treatment interferes with the function of Mfa fimbriae by reducing P. gingivalis adhesion to Streptococcus gordonii in a dual-species biofilm model. Finally, we show that treatment of bacteria with similar peptides inhibits extracellular polymerization of the Fim fimbriae, which are also expressed by P. gingivalis These results support a donor strand-based assembly mechanism for the P. gingivalis fimbriae and demonstrate the feasibility of using extracellular peptides to disrupt the biogenesis and function of these critical periodontal disease virulence factors. (Copyright © 2019 American Society for Microbiology.)
Databáze:	MEDLINE
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