Candida albicans cell-type switching and functional plasticity in the mammalian host

Key Points

  • Candida albicans is a ubiquitous fungal constituent of the mammalian gut, genitourinary and skin microbiota.

  • C. albicans can infect most human tissues and causes superficial and disseminated disease syndromes in both healthy and immunocompromised hosts.

  • C. albicans shares the ability to change shape in different environments with other fungi. At least nine different cell morphologies have been documented in this species.

  • Yeast can adopt several morphologies in addition to the standard white(a/α) morphology. White(a or α) and opaque(a or α) cells occur in a genetically distinct strain background, whereas the more recently reported opaque(a/α), grey and gastrointestinally induced transition (GUT) cell types occur in the predominant strain background. Similarly to the classic cell types, each yeast-like morphotype differs to some extent in cell shape, in vitro properties and interactions with the host.

  • Different C. albicans cell types vary in their ability to colonize the host or cause disease, as well as to inhabit different host niches. Metabolic differences seem to account for some of the differences in fitness.

  • C. albicans has introduced an unusual cell-type switch into its mating programme.

  • Researchers have identified numerous environmental (host) signals that trigger morphological transitions in C. albicans in vitro.

  • Signalling pathways in C. albicans transmit and integrate environmental information and induce morphological changes through fungal-specific transcription factors.

Abstract

Candida albicans is a ubiquitous commensal of the mammalian microbiome and the most prevalent fungal pathogen of humans. A cell-type transition between yeast and hyphal morphologies in C. albicans was thought to underlie much of the variation in virulence observed in different host tissues. However, novel yeast-like cell morphotypes, including opaque(a/α), grey and gastrointestinally induced transition (GUT) cell types, were recently reported that exhibit marked differences in vitro and in animal models of commensalism and disease. In this Review, we explore the characteristics of the classic cell types — yeast, hyphae, pseudohyphae and chlamydospores — as well as the newly identified yeast-like morphotypes. We highlight emerging knowledge about the associations of these different morphotypes with different host niches and virulence potential, as well as the environmental cues and signalling pathways that are involved in the morphological transitions.

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Figure 1: C. albicans cell type transitions.
Figure 2: C. albicans signalling and morphogenesis.
Figure 3: Opaque(a/α), grey and GUT cells.
Figure 4: The Efg1 and Wor1 transcription factors have central roles in Candida albicans morphological plasticity.

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Acknowledgements

The authors are grateful to H. Madhani for helpful comments regarding this Review. The laboratory of S.N. is supported by the US National Institutes of Health (grant R01AI108992), an Investigators in the Pathogenesis of Infectious Disease award from the Burroughs Wellcome Fund, and a Scholar in the Biomedical Sciences award from the Pew Charitable Trusts. In addition, B.A.G. is supported by the US National Science Foundation (grant 1144247) and J.W. is supported by the US National Institutes of Health (grant T32AI060537).

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Glossary

Budding

A form of asexual reproduction by yeast cells, in which a new cell develops as a focal outgrowth of the mother cell, followed by detachment once growth is complete.

Cytokinesis

Division of the cytoplasm between a mother cell and daughter cell after mitosis (or meiosis) is complete.

Suspensor cells

Terminal cells in mycelial networks that produce chlamydospores under nutrient-poor and oxygen-depleted conditions.

Thigmotropism

The ability of hyphal tip cells to alter the direction of polarized growth in response to irregularities in an underlying surface.

Meiosis

A type of cell division that produces four daughter cells, each containing half of the DNA content of the mother. This process is used to generate sexually competent cells such as a and α-cells in Saccharomyces cerevisiae.

Dimorphic fungi

A set of human fungal pathogens that grow as mycelia in the environment but as yeast (or spherules, in the case of Coccidioides immitis) in mammalian hosts. These pathogens include Blastomyces dermatitidis, C. immitis, Histoplasma capsulatum, Paracoccidioides brasiliensis, Talaromyces marneffei (formerly known as Penicillium marneffei) and Sporothrix schenckii.

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Noble, S., Gianetti, B. & Witchley, J. Candida albicans cell-type switching and functional plasticity in the mammalian host. Nat Rev Microbiol 15, 96–108 (2017). https://doi.org/10.1038/nrmicro.2016.157

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