Characterization of virulence properties in the C. parapsilosis sensu lato species

PLoS One. 2013 Jul 9;8(7):e68704. doi: 10.1371/journal.pone.0068704. Print 2013.

Abstract

The C. parapsilosis sensu lato group involves three closely related species, C. parapsilosis sensu stricto, C. orthopsilosis and C. metapsilosis. Although their overall clinical importance is dramatically increasing, there are few studies regarding the virulence properties of the species of the psilosis complex. In this study, we tested 63 C. parapsilosis sensu stricto, 12 C. metapsilosis and 18 C. orthopsilosis isolates for the ability to produce extracellular proteases, secrete lipases and form pseudohyphae. Significant differences were noted between species, with the C. metapsilosis strains failing to secrete lipase or to produce pseudohyphae. Nine different clinical isolates each of C. parapsilosis sensu stricto, C. orthopsilosis and C. metapsilosis were co-cultured with immortalized murine or primary human macrophages. C. parapsilosis sensu stricto isolates showed a significantly higher resistance to killing by primary human macrophages compared to C. orthopsilosis and C. metapsilosis isolates. In contrast, the killing of isolates by J774.2 mouse macrophages did not differ significantly between species. However, C. parapsilosis sensu stricto isolates induced the most damage to murine and human macrophages, and C. metapsilosis strains were the least toxic. Furthermore, strains that produced lipase or pseudohyphae were most resistant to macrophage-mediated killing and produced the most cellular damage. Finally, we used 9 isolates of each of the C. parapsilosis sensus lato species to examine their impact on the survival of Galleriamellonella larvae. The mortality rate of G. mellonella larvae infected with C. metapsilosis isolates was significantly lower than those infected with C. parapsilosis sensu stricto or C. orthopsilosis strains. Taken together, our findings demonstrate that C. metapsilosis is indeed the least virulent member of the psilosis group, and also highlight the importance of pseudohyphae and secreted lipases during fungal-host interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Candida / pathogenicity
  • Candida / physiology*
  • Cell Line
  • Host-Pathogen Interactions
  • Humans
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Leukocytes, Mononuclear / microbiology
  • Lipase / metabolism
  • Macrophages / immunology
  • Macrophages / metabolism
  • Macrophages / microbiology
  • Mice
  • Peptide Hydrolases / metabolism
  • Phagocytosis
  • Virulence
  • Virulence Factors / genetics

Substances

  • Virulence Factors
  • Lipase
  • Peptide Hydrolases

Grants and funding

NT was supported by the European Union and co-funded by the European Social Fund. Project number: TÁMOP-4.2.2/B-10/1-2010-0012. AG was supported in part by OTKA NF 84006 (http://www.otka.hu/en), NN100374 (ERA-Net PathoGenomics Program) (http://www.pathogenomics-era.net/) and an EMBO Installation Grant (http://www.embo.org/), JN was supported in part by an Irma T. Hirschl/Monique Weill-Caulier Trust Research Award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.