Glycation of Host Proteins Increases Pathogenic Potential of Porphyromonas gingivalis

International Journal of Molecular Sciences

Rosalind E. Jenkins¹  Jason L. Brown²  John W. Smalley²  Edwin A. Yates³  Michał Śmiga⁴  Teresa Olczak⁴  Paulina Ślęzak⁴  Klaudia Siemińska⁴ 

[1] CDSS Bioanalytical Facility, Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, Faculty of Health and Life Science, The University of Liverpool, Liverpool L69 3GE, UK;Institute of Life Course and Medical Sciences, School of Dentistry, The University of Liverpool, Pembroke Place, Liverpool L3 5PS, UK;Institute of Systems, Molecular and Integrative Biology, Faculty of Health and Life Science, The University of Liverpool, Liverpool L69 7ZB, UK;Laboratory of Medical Biology, Faculty of Biotechnology, University of Wrocław, 14A F. Joliot-Curie St., 50-383 Wrocław, Poland;

关键词: periodontitis;    diabetes;    glycation;    Porphyromonas gingivalis;    heme;    HmuY;   

DOI  :  10.3390/ijms222112084

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown