Trends in Microbiology
Volume 9, Issue 7, 1 July 2001, Pages 327-335
Journal home page for Trends in Microbiology

Review
Virulence factors of Candida albicans

https://doi.org/10.1016/S0966-842X(01)02094-7Get rights and content

Abstract

Candidiasis is a common infection of the skin, oral cavity and esophagus, gastrointestinal tract, vagina and vascular system of humans. Although most infections occur in patients who are immunocompromised or debilitated in some other way, the organism most often responsible for disease, Candida albicans, expresses several virulence factors that contribute to pathogenesis. These factors include host recognition biomolecules (adhesins), morphogenesis (the reversible transition between unicellular yeast cells and filamentous, growth forms), secreted aspartyl proteases and phospholipases. Additionally, ‘phenotypic switching’ is accompanied by changes in antigen expression, colony morphology and tissue affinities in C. albicans and several other Candida spp. Switching might provide cells with a flexibility that results in the adaptation of the organism to the hostile conditions imposed not only by the host but also by the physician treating the infection.

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

  • Are the virulence factors required for disease development also required for commensalism?

  • Are there other examples of site-specific (anatomical) expression of virulence factors?

  • What are the signal transduction pathways that regulate adhesin and degradative enzyme expression?

  • 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?

  • 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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