title: Degradation of human kininogens with the release of kinin peptides by extracellular proteinases of Candida spp.
abstract: The secretion of proteolytic enzymes by pathogenic microorganisms is one of the most successful strategies used by pathogens to colonize and infect the host organism. The extracellular microbial proteinases can seriously deregulate the homeostatic proteolytic cascades of the host, including the kinin-forming system, repeatedly reported to be activated during bacterial infection. The current study assigns a kinin-releasing activity to secreted proteinases of Candida spp. yeasts, the major fungal pathogens of humans. Of several Candida species studied, C. parapsilosis and C. albicans in their invasive filamentous forms are shown to produce proteinases which most effectively degrade proteinaceous kinin precursors, the kininogens. These enzymes, classified as aspartyl proteinases, have the highest kininogen-degrading activity at low pH (approx. 3.5), but the associated production of bradykinin-related peptides from a small fraction of kininogen molecules is optimal at neutral pH (6.5). The peptides effectively interact with cellular B2-type kinin receptors. Moreover, kinin-related peptides capable of interacting with inflammation-induced B1-type receptors are also formed, but with a reversed pH dependence. The presented variability of the potential extracellular kinin production by secreted aspartyl proteinases of Candida spp. is consistent with the known adaptability of these opportunistic pathogens to different niches in the host organism.
authors.affiliation: Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Rapala-Kozik
authors.forename: Justyna
authors.initials: J
authors.lastname: Karkowska-Kuleta
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Ryzanowska
authors.forename: Anna
authors.initials: A
authors.lastname: Golda
authors.forename: Anna
authors.initials: A
authors.lastname: Barbasz
authors.forename: Alexander
authors.initials: A
authors.lastname: Faussner
authors.forename: Andrzej
authors.initials: A
authors.lastname: Kozik
mesh_terms: D002175:Candida / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D007704:Kininogens / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism*
chemical_list: D007704:Kininogens; D010447:Peptide Hydrolases