Glycation of Host Proteins Increases Pathogenic Potential of <i>Porphyromonas gingivalis</i>

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...

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Autores principales:	Michał Śmiga, John W. Smalley, Paulina Ślęzak, Jason L. Brown, Klaudia Siemińska, Rosalind E. Jenkins, Edwin A. Yates, Teresa Olczak
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	periodontitis diabetes glycation <i>Porphyromonas gingivalis</i> heme HmuY Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/d0c6fa6669a445a9babe3ca49a032b35
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spelling	oai:doaj.org-article:d0c6fa6669a445a9babe3ca49a032b352021-11-11T17:28:25ZGlycation of Host Proteins Increases Pathogenic Potential of <i>Porphyromonas gingivalis</i>10.3390/ijms2221120841422-00671661-6596https://doaj.org/article/d0c6fa6669a445a9babe3ca49a032b352021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/12084https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067The 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 <i>Porphyromonas gingivalis</i> in mediating the disease process. The aim of this study was to determine whether glycated proteins are more easily utilized by <i>P. gingivalis</i> 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 <i>P. gingivalis</i> cells or HmuY protein was examined using spectroscopic methods, SDS-PAGE and co-culturing <i>P. gingivalis</i> with human keratinocytes. We found that glycation increases the ability of <i>P. gingivalis</i> 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 <i>P. gingivalis</i> by making heme more available from hemoglobin and facilitating bacterial biofilm formation, thus increasing <i>P. gingivalis</i> pathogenic potential in vivo.Michał ŚmigaJohn W. SmalleyPaulina ŚlęzakJason L. BrownKlaudia SiemińskaRosalind E. JenkinsEdwin A. YatesTeresa OlczakMDPI AGarticleperiodontitisdiabetesglycation<i>Porphyromonas gingivalis</i>hemeHmuYBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12084, p 12084 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	periodontitis diabetes glycation <i>Porphyromonas gingivalis</i> heme HmuY Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	periodontitis diabetes glycation <i>Porphyromonas gingivalis</i> heme HmuY Biology (General) QH301-705.5 Chemistry QD1-999 Michał Śmiga John W. Smalley Paulina Ślęzak Jason L. Brown Klaudia Siemińska Rosalind E. Jenkins Edwin A. Yates Teresa Olczak Glycation of Host Proteins Increases Pathogenic Potential of <i>Porphyromonas gingivalis</i>
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 <i>Porphyromonas gingivalis</i> in mediating the disease process. The aim of this study was to determine whether glycated proteins are more easily utilized by <i>P. gingivalis</i> 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 <i>P. gingivalis</i> cells or HmuY protein was examined using spectroscopic methods, SDS-PAGE and co-culturing <i>P. gingivalis</i> with human keratinocytes. We found that glycation increases the ability of <i>P. gingivalis</i> 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 <i>P. gingivalis</i> by making heme more available from hemoglobin and facilitating bacterial biofilm formation, thus increasing <i>P. gingivalis</i> pathogenic potential in vivo.
format	article
author	Michał Śmiga John W. Smalley Paulina Ślęzak Jason L. Brown Klaudia Siemińska Rosalind E. Jenkins Edwin A. Yates Teresa Olczak
author_facet	Michał Śmiga John W. Smalley Paulina Ślęzak Jason L. Brown Klaudia Siemińska Rosalind E. Jenkins Edwin A. Yates Teresa Olczak
author_sort	Michał Śmiga
title	Glycation of Host Proteins Increases Pathogenic Potential of <i>Porphyromonas gingivalis</i>
title_short	Glycation of Host Proteins Increases Pathogenic Potential of <i>Porphyromonas gingivalis</i>
title_full	Glycation of Host Proteins Increases Pathogenic Potential of <i>Porphyromonas gingivalis</i>
title_fullStr	Glycation of Host Proteins Increases Pathogenic Potential of <i>Porphyromonas gingivalis</i>
title_full_unstemmed	Glycation of Host Proteins Increases Pathogenic Potential of <i>Porphyromonas gingivalis</i>
title_sort	glycation of host proteins increases pathogenic potential of <i>porphyromonas gingivalis</i>
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/d0c6fa6669a445a9babe3ca49a032b35
work_keys_str_mv	AT michałsmiga glycationofhostproteinsincreasespathogenicpotentialofiporphyromonasgingivalisi AT johnwsmalley glycationofhostproteinsincreasespathogenicpotentialofiporphyromonasgingivalisi AT paulinaslezak glycationofhostproteinsincreasespathogenicpotentialofiporphyromonasgingivalisi AT jasonlbrown glycationofhostproteinsincreasespathogenicpotentialofiporphyromonasgingivalisi AT klaudiasieminska glycationofhostproteinsincreasespathogenicpotentialofiporphyromonasgingivalisi AT rosalindejenkins glycationofhostproteinsincreasespathogenicpotentialofiporphyromonasgingivalisi AT edwinayates glycationofhostproteinsincreasespathogenicpotentialofiporphyromonasgingivalisi AT teresaolczak glycationofhostproteinsincreasespathogenicpotentialofiporphyromonasgingivalisi
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Glycation of Host Proteins Increases Pathogenic Potential of <i>Porphyromonas gingivalis</i>

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