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

Acta Biochim Pol. 2017;64(3):391-400. doi: 10.18388/abp.2017_1609. Epub 2017 Jun 24.

Abstract

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 the host organism by interfering with functionality of these systems or by exploiting specific activity of the bound enzymes. Aim of the study presented here 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 have 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 ability of the 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 the HPG binding and in a range of 10-8-10-9 M for the 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.

Keywords: candidiasis; cell wall proteins; contact system; fibrinolysis.

MeSH terms

  • Binding, Competitive
  • Candida parapsilosis / metabolism*
  • Candida parapsilosis / pathogenicity
  • Cell Wall / metabolism
  • Chromatography, Affinity
  • Fungal Proteins / isolation & purification
  • Fungal Proteins / metabolism*
  • Host-Pathogen Interactions
  • Humans
  • Hyphae / metabolism
  • Kinetics
  • Kininogen, High-Molecular-Weight / metabolism*
  • Kininogens / metabolism
  • Plasminogen / metabolism*
  • Thermodynamics

Substances

  • Fungal Proteins
  • KNG1 protein, human
  • Kininogen, High-Molecular-Weight
  • Kininogens
  • Plasminogen