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Peptidylarginine Deiminase Isozyme-Specific PAD2, PAD3 and PAD4 Inhibitors Differentially Modulate Extracellular Vesicle Signatures and Cell Invasion in Two Glioblastoma Multiforme Cell Lines
Open AccessArticle

Peptidylarginine Deiminase of Porphyromonas gingivalis Modulates the Interactions between Candida albicans Biofilm and Human Plasminogen and High-Molecular-Mass Kininogen

1
Department of Comparative Biochemistry and Bioanalytics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Gronostajowa 7, 30-387 Krakow, Poland
2
Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Gronostajowa 7, 30-387 Krakow, Poland
3
Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, 501 S. Preston St, Louisville, KY 40202, USA
4
Department of Analytical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Gronostajowa 7, 30-387 Krakow, Poland
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(7), 2495; https://doi.org/10.3390/ijms21072495
Received: 31 December 2019 / Revised: 23 March 2020 / Accepted: 1 April 2020 / Published: 3 April 2020
Microorganisms that create mixed-species biofilms in the human oral cavity include, among others, the opportunistic fungus Candida albicans and the key bacterial pathogen in periodontitis, Porphyromonas gingivalis. Both species use arsenals of virulence factors to invade the host organism and evade its immune system including peptidylarginine deiminase that citrullinates microbial and host proteins, altering their function. We assessed the effects of this modification on the interactions between the C. albicans cell surface and human plasminogen and kininogen, key components of plasma proteolytic cascades related to the maintenance of hemostasis and innate immunity. Mass spectrometry was used to identify protein citrullination, and microplate tests to quantify the binding of modified plasminogen and kininogen to C. albicans cells. Competitive radioreceptor assays tested the affinity of citrullinated kinins to their specific cellular receptors. The citrullination of surface-exposed fungal proteins reduced the level of unmodified plasminogen binding but did not affect unmodified kininogen binding. However, the modification of human proteins did not disrupt their adsorption to the unmodified fungal cells. In contrast, the citrullination of kinins exerted a significant impact on their interactions with cellular receptors reducing their affinity and thus affecting the role of kinin peptides in the development of inflammation. View Full-Text
Keywords: biofilm; plasminogen; kininogen; kinins; candidiasis; periodontitis; citrullination biofilm; plasminogen; kininogen; kinins; candidiasis; periodontitis; citrullination
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Karkowska-Kuleta, J.; Surowiec, M.; Gogol, M.; Koziel, J.; Potempa, B.; Potempa, J.; Kozik, A.; Rapala-Kozik, M. Peptidylarginine Deiminase of Porphyromonas gingivalis Modulates the Interactions between Candida albicans Biofilm and Human Plasminogen and High-Molecular-Mass Kininogen. Int. J. Mol. Sci. 2020, 21, 2495.

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