Functional characterization of secreted aspartyl proteases in Candida parapsilosis

Dhirendra Kumar Singh, Tibor Németh, Alexandra Papp, Renáta Tóth, Szilvia Lukácsi, Olga Heidingsfeld, Jiri Dostal, Csaba Vágvölgyi, Zsuzsa Bajtay, Mihály Józsi, Attila Gácser

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Abstract

Candida parapsilosis is an emerging non-albicans Candida species that largely affects low-birth-weight infants and immunocompromised patients. Fungal pathogenesis is promoted by the dynamic expression of diverse virulence factors, with secreted proteolytic enzymes being linked to the establishment and progression of disease. Although secreted aspartyl proteases (Sap) are critical for Candida albicans pathogenicity, their role in C. parapsilosis is poorly elucidated. In the present study, we aimed to examine the contribution of C. parapsilosis SAPP genes SAPP1, SAPP2, and SAPP3 to the virulence of the species. Our results indicate that SAPP1 and SAPP2, but not SAPP3, influence adhesion, host cell damage, phagosomelysosome maturation, phagocytosis, killing capacity, and cytokine secretion by human peripheral blood-derived macrophages. Purified Sapp1p and Sapp2p were also shown to efficiently cleave host complement component 3b (C3b) and C4b proteins and complement regulator factor H. Additionally, Sapp2p was able to cleave factor H-related protein 5 (FHR-5). Altogether, these data demonstrate the diverse, significant contributions that SAPP1 and SAPP2 make to the establishment and progression of disease by C. parapsilosis through enabling the attachment of the yeast cells to mammalian cells and modulating macrophage biology and disruption of the complement cascade.

Original languageEnglish
Article numbere00484-19
JournalmSphere
Volume4
Issue number4
DOIs
Publication statusPublished - Jan 1 2019

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Keywords

  • Candida parapsilosis
  • Complement
  • Host-pathogen interactions
  • Proteases
  • Virulence

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

Cite this

Singh, D. K., Németh, T., Papp, A., Tóth, R., Lukácsi, S., Heidingsfeld, O., Dostal, J., Vágvölgyi, C., Bajtay, Z., Józsi, M., & Gácser, A. (2019). Functional characterization of secreted aspartyl proteases in Candida parapsilosis. mSphere, 4(4), [e00484-19]. https://doi.org/10.1128/mSphere.00484-19