Glycation of host proteins increases pathogenic potential of Porphyromonas gingivalis

Śmiga, M., Smalley, J. W., Ślęzak, P., Brown, J. L. , Siemińska, K., Jenkins, R. E., Yates, E. A. and Olczak, T. (2021) Glycation of host proteins increases pathogenic potential of Porphyromonas gingivalis. International Journal of Molecular Sciences, 22(21), 12084. (doi: 10.3390/ijms222112084) (PMID:34769513) (PMCID:PMC8585099)

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 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.

• Item Type: Articles
• Additional Information: This research was funded by the National Science Center (NCN, Krakow, Poland), grant number 2016/23/B/NZ6/00080 (to T.O.). Open access publication cost was financed by the “Excellence Initiative–Research University” program for University of Wrocław, Poland, for years 2020–2026.
• Keywords: Periodontitis, diabetes, glycation, Porphyromonas gingivalis, heme, HmuY, hemoglobin, albumin, collagen, pathogenesis.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Brown, Dr Jason

Creator Roles

Brown, J. L.: Investigation

• Authors: Śmiga, M., Smalley, J. W., Ślęzak, P., Brown, J. L., Siemińska, K., Jenkins, R. E., Yates, E. A., and Olczak, T.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
• Journal Name: International Journal of Molecular Sciences
• Publisher: MDPI
• ISSN: 1661-6596
• ISSN (Online): 1422-0067
• Published Online: 08 November 2021
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in International Journal of Molecular Sciences 22(21): 12084
• Publisher Policy: Reproduced under a Creative Commons License