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



Smiga, Michal, Smalley, John W, Slezak, Paulina, Brown, Jason L, Sieminska, Klaudia, Jenkins, Rosalind E, Yates, Edwin A ORCID: 0000-0001-9365-5433 and Olczak, Teresa
(2021) Glycation of Host Proteins Increases Pathogenic Potential of <i>Porphyromonas gingivalis</i>. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 22 (21). 12084-.

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: periodontitis, diabetes, glycation, Porphyromonas gingivalis, heme, HmuY, hemoglobin, albumin, collagen, pathogenesis
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 15 Nov 2021 11:27
Last Modified: 07 Feb 2024 13:25
DOI: 10.3390/ijms222112084
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3143193