Trends in Microbiology
ReviewVirulence factors of Candida albicans
Section snippets
The virulence factors of C. albicans: detection methods
The major breakthrough in assessing the contribution of specific genes to virulence occurred when transformation protocols for C. albicans were developed along with techniques that could be used to delete both alleles of a specific gene sequentially. Before discussing the current views on virulence in this organism, we will briefly describe the methods used to transform and disrupt genes in C. albicans.
C. albicans poses special problems for those scientists interested in studying gene function
Virulence factors: what are they?
Like other pathogens, virulence in C. albicans includes host recognition. Binding of the organism to host cells, host cell proteins or microbial competitors (co-aggregation) more than likely prevents or at least reduces the extent of clearance by the host. Additionally, several degradative enzymes have been shown to promote virulence. Intuitively, invasion should be facilitated by the transition between yeast cells and filamentous growth (morphogenesis) in comparison to isotropic growth
Enzymes that contribute to invasiveness
The secreted aspartyl proteinases (SAP) and phospholipases (PL) are two rather large families of C. albicans enzymes, some of which have been associated with virulence (Fig. 1). Of the four PLs identified thus far (PLA, PLB, PLC and PLD), only PLB1 has been shown to be required for virulence in an animal model of candidiasis; a gene-deleted strain produced less phospholipase in vitro and was less virulent (40% killing versus 100% by wild-type cells) 62. Plb1p activity has recently been detected
Phenotypic switching
Pomes et al. demonstrated that low doses of UV light resulted in the formation of rough colonies of C. albicans at high frequencies (3 × 10−3), and that the reversion of this phenotype to the original smooth colony occurred at a frequency as high as 9 × 10−4 (Ref. 73). Therefore, the switching in colony phenotypes was reversible and occurred at high frequencies. Slutsky et al. using strain 3153A extended these observations and found that additional colony types could be observed, including
Summary
The human pathogen Candida albicans is successful both as a commensal and as a pathogen. It is clear that C. albicans utilizes several genes whose expression is required for virulence. Importantly, the expression of many of these genes, including PHR1, PHR2 and CHK1, could be specific for anatomical sites. Nevertheless, the repertoire of virulence attributes of the organism includes host-recognition proteins (adhesins), transitional growth, proteolytic and lipolytic enzymes and probably
Questions for future research
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Are the virulence factors required for disease development also required for commensalism?
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Are there other examples of site-specific (anatomical) expression of virulence factors?
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What are the signal transduction pathways that regulate adhesin and degradative enzyme expression?
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C. albicans-specific genes have been found to include many with a catabolic function. What is the relationship of some (or all) of them to disease development?
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Given the variability of the C. albicans genome, what influence
Acknowledgements
We wish to acknowledge the National Institutes of Health (NIH-NIAID) and The Burroughs Wellcome Fund for their generous support through research grants.
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