Abstract
BackgroundInvasion of host tissue by the human fungal pathogen Candida albicans is an important step during the development of candidosis. However, not all C. albicans strains possess the same invasive and virulence properties. For example, the two clinical isolates SC5314 and ATCC10231 differ in their ability to invade host tissue and cause experimental infections. Strain SC5314 is invasive whereas strain ATCC10231 is non-invasive and strongly attenuated in virulence compared to SC5314. In this study we compare the in vitro phenotypic, transcriptional and genomic profiles of these two widely used laboratory strains in order to determine the principal biological and genetic properties responsible for their differential virulence.ResultsIn all media tested, the two strains showed the same metabolic flexibility, stress resistance, adhesion properties and hydrolytic enzyme secretion in vitro. However, differences were observed in response to cell-surface disturbing agents and alkaline pH. Furthermore, reduced hyphal formation in strain ATCC10231 under certain conditions correlated with reduced invasive properties in an in vitro invasion assay and a reduced ability to invade epithelial tissue. Despite these diverse phenotypic properties, no substantial genomic differences were detected by comparative genome hybridisation within the open reading frames. However, in vitro transcriptional profiling displayed major differences in the gene expression of these two strains, even under normal in vitro growth conditions.ConclusionOur data suggest that the reason for differential virulence of C. albicans strains is not due to the absence of specific genes, but rather due to differences in the expression, function or activity of common genes.
Highlights
Invasion of host tissue by the human fungal pathogen Candida albicans is an important step during the development of candidosis
Phenotypic comparison of SC5314 and ATCC10231 Characteristics such as growth rate are likely to have an impact on the pathogenicity of different C. albicans strains
It is known from the literature that strain ATCC10231 is non-invasive in an intraperitoneal infection model in vivo [32] and our own investigations showed that this particular strain is non-invasive in an ex vivo infection model [33] as well as in an in vitro invasion model using extracellular matrix [13]
Summary
Invasion of host tissue by the human fungal pathogen Candida albicans is an important step during the development of candidosis. Secreted hydrolytic enzymes may aid the fungus during invasion by destroying host cell surface components and immune factors or by extracting nutrients for the fungus [8] Among these hydrolases are secreted aspartic proteases (Saps), phospholipases (Plbs) and lipases (Lips) [9]. It has been proposed that yeast cells are more suitable for dissemination whereas hyphal forms play a key role during invasion [10] Supporting this view, most mutants which have reduced abilities to undergo the yeast to hyphal transition are attenuated in a wide range of infection models [1,11,12,13]. It has been shown that the correct sensing of extracellular pH is a prerequisite for hyphal formation and virulence under alkaline conditions and during systemic infections [13,17,18]
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