Cargando…

Glycation of Host Proteins Increases Pathogenic Potential of Porphyromonas gingivalis

The non-enzymatic addition of glucose (glycation) to circulatory and tissue proteins is a ubiquitous pathophysiological consequence of hyperglycemia in diabetes. Given the high incidence of periodontitis and diabetes and the emerging link between these conditions, it is of crucial importance to defi...

Descripción completa

Detalles Bibliográficos
Autores principales: Śmiga, Michał, Smalley, John W., Ślęzak, Paulina, Brown, Jason L., Siemińska, Klaudia, Jenkins, Rosalind E., Yates, Edwin A., Olczak, Teresa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8585099/
https://www.ncbi.nlm.nih.gov/pubmed/34769513
http://dx.doi.org/10.3390/ijms222112084
_version_ 1784597609731588096
author Śmiga, Michał
Smalley, John W.
Ślęzak, Paulina
Brown, Jason L.
Siemińska, Klaudia
Jenkins, Rosalind E.
Yates, Edwin A.
Olczak, Teresa
author_facet Śmiga, Michał
Smalley, John W.
Ślęzak, Paulina
Brown, Jason L.
Siemińska, Klaudia
Jenkins, Rosalind E.
Yates, Edwin A.
Olczak, Teresa
author_sort Śmiga, Michał
collection PubMed
description The non-enzymatic addition of glucose (glycation) to circulatory and tissue proteins is a ubiquitous pathophysiological consequence of hyperglycemia in diabetes. Given the high incidence of periodontitis and diabetes and the emerging link between these conditions, it is of crucial importance to define the basic virulence mechanisms employed by periodontopathogens such as Porphyromonas gingivalis in mediating the disease process. The aim of this study was to determine whether glycated proteins are more easily utilized by P. gingivalis to stimulate growth and promote the pathogenic potential of this bacterium. We analyzed the properties of three commonly encountered proteins in the periodontal environment that are known to become glycated and that may serve as either protein substrates or easily accessible heme sources. In vitro glycated proteins were characterized using colorimetric assays, mass spectrometry, far- and near-UV circular dichroism and UV–visible spectroscopic analyses and SDS-PAGE. The interaction of glycated hemoglobin, serum albumin and type one collagen with P. gingivalis cells or HmuY protein was examined using spectroscopic methods, SDS-PAGE and co-culturing P. gingivalis with human keratinocytes. We found that glycation increases the ability of P. gingivalis to acquire heme from hemoglobin, mostly due to heme sequestration by the HmuY hemophore-like protein. We also found an increase in biofilm formation on glycated collagen-coated abiotic surfaces. We conclude that glycation might promote the virulence of P. gingivalis by making heme more available from hemoglobin and facilitating bacterial biofilm formation, thus increasing P. gingivalis pathogenic potential in vivo.
format Online
Article
Text
id pubmed-8585099
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-85850992021-11-12 Glycation of Host Proteins Increases Pathogenic Potential of Porphyromonas gingivalis Śmiga, Michał Smalley, John W. Ślęzak, Paulina Brown, Jason L. Siemińska, Klaudia Jenkins, Rosalind E. Yates, Edwin A. Olczak, Teresa Int J Mol Sci Article The non-enzymatic addition of glucose (glycation) to circulatory and tissue proteins is a ubiquitous pathophysiological consequence of hyperglycemia in diabetes. Given the high incidence of periodontitis and diabetes and the emerging link between these conditions, it is of crucial importance to define the basic virulence mechanisms employed by periodontopathogens such as Porphyromonas gingivalis in mediating the disease process. The aim of this study was to determine whether glycated proteins are more easily utilized by P. gingivalis to stimulate growth and promote the pathogenic potential of this bacterium. We analyzed the properties of three commonly encountered proteins in the periodontal environment that are known to become glycated and that may serve as either protein substrates or easily accessible heme sources. In vitro glycated proteins were characterized using colorimetric assays, mass spectrometry, far- and near-UV circular dichroism and UV–visible spectroscopic analyses and SDS-PAGE. The interaction of glycated hemoglobin, serum albumin and type one collagen with P. gingivalis cells or HmuY protein was examined using spectroscopic methods, SDS-PAGE and co-culturing P. gingivalis with human keratinocytes. We found that glycation increases the ability of P. gingivalis to acquire heme from hemoglobin, mostly due to heme sequestration by the HmuY hemophore-like protein. We also found an increase in biofilm formation on glycated collagen-coated abiotic surfaces. We conclude that glycation might promote the virulence of P. gingivalis by making heme more available from hemoglobin and facilitating bacterial biofilm formation, thus increasing P. gingivalis pathogenic potential in vivo. MDPI 2021-11-08 /pmc/articles/PMC8585099/ /pubmed/34769513 http://dx.doi.org/10.3390/ijms222112084 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Śmiga, Michał
Smalley, John W.
Ślęzak, Paulina
Brown, Jason L.
Siemińska, Klaudia
Jenkins, Rosalind E.
Yates, Edwin A.
Olczak, Teresa
Glycation of Host Proteins Increases Pathogenic Potential of Porphyromonas gingivalis
title Glycation of Host Proteins Increases Pathogenic Potential of Porphyromonas gingivalis
title_full Glycation of Host Proteins Increases Pathogenic Potential of Porphyromonas gingivalis
title_fullStr Glycation of Host Proteins Increases Pathogenic Potential of Porphyromonas gingivalis
title_full_unstemmed Glycation of Host Proteins Increases Pathogenic Potential of Porphyromonas gingivalis
title_short Glycation of Host Proteins Increases Pathogenic Potential of Porphyromonas gingivalis
title_sort glycation of host proteins increases pathogenic potential of porphyromonas gingivalis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8585099/
https://www.ncbi.nlm.nih.gov/pubmed/34769513
http://dx.doi.org/10.3390/ijms222112084
work_keys_str_mv AT smigamichał glycationofhostproteinsincreasespathogenicpotentialofporphyromonasgingivalis
AT smalleyjohnw glycationofhostproteinsincreasespathogenicpotentialofporphyromonasgingivalis
AT slezakpaulina glycationofhostproteinsincreasespathogenicpotentialofporphyromonasgingivalis
AT brownjasonl glycationofhostproteinsincreasespathogenicpotentialofporphyromonasgingivalis
AT sieminskaklaudia glycationofhostproteinsincreasespathogenicpotentialofporphyromonasgingivalis
AT jenkinsrosalinde glycationofhostproteinsincreasespathogenicpotentialofporphyromonasgingivalis
AT yatesedwina glycationofhostproteinsincreasespathogenicpotentialofporphyromonasgingivalis
AT olczakteresa glycationofhostproteinsincreasespathogenicpotentialofporphyromonasgingivalis