<it>Candida albicans SUR7 </it>contributes to secretion, biofilm formation, and macrophage killing

<p>Abstract</p> <p>Background</p> <p><it>Candida albicans SUR7 </it>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 <it>C. albicans </it>homolog of the <it>Saccharomyces cerevisiae </it>endocytosis-related protein Sur7p. We therefore generated a <it>C. albicans sur7</it>Δ null mutant and examined its contribution to key virulence attributes.</p> <p>Results</p> <p>Structurally, the <it>C. albicans sur7</it>Δ 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 <it>SUR7 </it>resulted in a temperature-sensitive growth defect at high temperatures (42°C), which was partially rescued by addition of NaCl. We next examined the role of the <it>SUR7 </it>paralog <it>C. albicans FMP45 </it>in this temperature-sensitive phenotype. Analysis of <it>C. albicans </it>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 <it>C. albicans sur7</it>Δ 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 <it>sur7</it>Δ mutant demonstrated increased adhesion to polystyrene and of note, was markedly defective in biofilm formation. In an <it>in vitro </it>macrophage model of virulence, the <it>sur7</it>Δ mutant was impaired in macrophage killing.</p> <p>Conclusions</p> <p>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 <it>C. albicans sur7</it>Δ mutant.</p>