Binding of human plasminogen and high-molecular-mass kininogen by cell surface-exposed proteins of Candida parapsilosis

  • Justyna Karkowska-Kuleta Department of Comparative Biochemistry and Bioanalytics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Gronostajowa 7, 30-387 Krakow, Poland
  • Dorota Zajac Department of Analytical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Gronostajowa 7, 30-387 Krakow, Poland
  • Grazyna Bras Department of Comparative Biochemistry and Bioanalytics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Gronostajowa 7, 30-387 Krakow, Poland
  • Oliwia Bochenska Department of Analytical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Gronostajowa 7, 30-387 Krakow, Poland
  • Maria Rapala-Kozik Department of Comparative Biochemistry and Bioanalytics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Gronostajowa 7, 30-387 Krakow, Poland
  • Andrzej Kozik Department of Analytical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Gronostajowa 7, 30-387 Krakow, Poland


Pathogenic microbes can recruit to their cell surface human proteins that are components of important proteolytic cascades involved in coagulation, fibrinolysis and innate immune response. Once located at the bacterial or fungal surface such deployed proteins might be utilized by pathogens to facilitate invasion and dissemination within host organism by interfering with functionality of these systems or by exploiting specific activity of bound enzymes.

            The aim of the present study was to characterize this phenomenon in Candida parapsilosis (Ashford) Langeron et Talice ― an important causative agent of systemic fungal infections (candidiases and candidemias) in humans. We investigated the interactions of fungal surface-exposed proteins with plasminogen (HPG) and high-molecular-mass kininogen (HK) ― the crucial components of human fibrinolytic system and proinflammatory/procoagulant contact-activated kinin-forming system, respectively.

            After confirming an ability of fungal surface-exposed proteins to bind HPG and HK, four of them ― two agglutinin-like sequence (Als) proteins CPAR2_404780 and CPAR2_404800, a heat shock protein Ssa2 and a moonlighting protein 6-phosphogluconate dehydrogenase 1 ― were purified using ion-exchange chromatography, gel filtration and chromatofocusing. Then, their affinities to HPG and HK were characterized with surface plasmon resonance measurements. The determined dissociation constants for the investigated protein-protein complexes were within a 10–7 M order for HPG binding and in a range of 10–8-10–9 M for HK binding.

Detailed characterization of adsorption of these two important plasma proteins on the fungal cell surface may help to increase our understanding of molecular mechanisms of C. parapsilosis-dependent candidiasis.


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