Candida albicans SUR7 contributes to secretion, biofilm formation, and macrophage killing

BMC Microbiol. 2010 Apr 30;10:133. doi: 10.1186/1471-2180-10-133.

Abstract

Background: Candida albicans SUR7 has been shown to be required for plasma membrane organization and cell wall synthesis, but its role in virulence is not known. Using a bioinformatics strategy, we previously identified several novel putative secretion pathway proteins potentially involved in virulence, including the C. albicans homolog of the Saccharomyces cerevisiae endocytosis-related protein Sur7p. We therefore generated a C. albicans sur7Delta null mutant and examined its contribution to key virulence attributes.

Results: Structurally, the C. albicans sur7Delta mutant was impaired in response to filamentation-inducing conditions, and formed aberrant hyphae with extensive accumulation of plasma membrane-derived structures within the cell. Absence of SUR7 resulted in a temperature-sensitive growth defect at high temperatures (42 degrees C), which was partially rescued by addition of NaCl. We next examined the role of the SUR7 paralog C. albicans FMP45 in this temperature-sensitive phenotype. Analysis of C. albicans Fmp45p-GFP demonstrated co-localization of Fmp45p with Sur7p and increased fluorescence in the plasma membrane in the presence of high salt. We next focused on key virulence-related phenotypes. The C. albicans sur7Delta null mutant exhibited secretory defects: reduced lipase secretion, and increased levels of secreted Sap2p. The null mutant was hyper-susceptible to sub-inhibitory concentrations of caspofungin, but not amphotericin B and 5-fluorocytosine. Functionally, the sur7Delta mutant demonstrated increased adhesion to polystyrene and of note, was markedly defective in biofilm formation. In an in vitro macrophage model of virulence, the sur7Delta mutant was impaired in macrophage killing.

Conclusions: Plasma membrane and cell wall organization are important for cell morphology, and alterations of these structures contributed to impairment of several key virulence-associated phenotypes in the C. albicans sur7Delta mutant.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Biofilms / growth & development*
  • Candida albicans / growth & development
  • Candida albicans / metabolism
  • Candida albicans / pathogenicity
  • Candida albicans / physiology*
  • Cell Death*
  • Cell Line
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Fungal Proteins / physiology*
  • Gene Deletion
  • Hot Temperature
  • Hyphae / cytology
  • Hyphae / growth & development
  • Macrophages / microbiology*
  • Membrane Proteins / genetics
  • Mice
  • Saccharomyces cerevisiae Proteins / genetics
  • Sodium Chloride / metabolism
  • Virulence
  • Virulence Factors / genetics
  • Virulence Factors / physiology*

Substances

  • Fungal Proteins
  • Membrane Proteins
  • SUR7 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Virulence Factors
  • Sodium Chloride