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Origins of variation in the fungal cell surface

Nature Reviews Microbiology volume 2, pages 533–540 (2004)Cite this article

Key Points

  • This review examines the genetic mechanisms that underlie fungal adhesion to surfaces. The authors propose a common mechanism for the generation of diversity among fungal adhesins. They suggest that amplification and contraction of the repeats found in the adhesin genes creates the diversity seen in these proteins. Adhesion is a key component of fungal virulence, so an understanding of fungal adhesion mechanisms is also medically important.

  • Saccharomyces cerevisiae is ideally suited to studying the structure and function of adhesin-family genes. There are five adhesin genes, known as FLO genes, in S. cerevisiae, although only one allele is usually expressed. The chromosomal locations of each of the FLO genes and the phenotypes associated with their overexpression are described.

  • Recombination within and between FLO genes can generate cell-surface diversity. Sequence motifs within each FLO gene are repeated so that recombination can occur between tandem repeats in a single adhesin gene or between different genes. Certain motifs are highly conserved and the authors suggest that one reason for this might be that recombination to generate surface-antigen diversity might provide a selective advantage.

  • Differential expression of the FLO alleles also contributes to cell-wall diversity. FLO11, the only FLO gene that is expressed in vegetative S. cerevisiae in vitro, is switched on and off by an epigenetic mechanism that involves chromatin-binding proteins. These are modulated through nutritional signals that are transmitted through mitogen-activated protein kinase and protein kinase A pathways.

  • It is not known how silent FLO genes become transcriptionally activated in vivo, but certain mutations can switch on the expression of these genes. This might also be a feature of Candida glabrata, which usually expresses only one of five adhesin genes. However, in Candida albicans a more complex system has been reported, in which more than one adhesin gene is expressed concurrently.

  • The authors discuss the roles that the adhesin loci of S. cerevisiae and Candida spp. have in the establishment and maintenance of fungal biofilms and in infection.

Abstract

The increase in hospital-acquired fungal infections has been attributed to the ability of fungi to adhere not only to human tissues, but also to the plastic prostheses and invasive devices that are used to treat disease. These properties are conferred by a family of fungal cell-surface proteins, called adhesins. Adhesins might also have a central role in the formation of fungal biofilms, which are resistant to antimicrobial drugs. The structure of the genes that encode adhesin-family members, and the sequence homology between them, enables genetic reshuffling of domains to form new genes. Coupled with epigenetic changes in gene expression, these genetic rearrangements provide a reservoir of cell-surface molecules with new functions.

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Figure 1: Chromosomal localization of adhesin genes and pseudogenes in the Saccharomyces cerevisiae laboratory strain S288C.
Figure 2: Domain structure of adhesins.
Figure 3: Repeated nucleotide motifs in the FLO genes.
Figure 4: The conserved nucleotide sequence of motif 4 of the FLO genes.
Figure 5: The low level of conservation of third-position nucleotides in nucleotide motif 1 of FLO10.
Figure 6: Recombination between repeated DNA motifs in adhesin genes generates new alleles.
Figure 7: Saccharomyces cerevisiae FLO11 is required for adhesion to plastic and film formation.

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Acknowledgements

The authors thank F. Lewitter for her assistance with sequence analysis and S. Bumgarner for valuable discussions and proofreading of the manuscript. K.J.V. is a D. Collen Fellow of the Belgian American Educational Foundation and a beneficiary of a long-term travel grant from the Fund for Scientific Research — Flanders (F.W.O. Vlaanderen). G.R.F. is an American Cancer Society Professor of Genetics. Research in G.R.F.'s laboratory was supported by a National Institutes of Health grant.

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Authors and Affiliations

  1. Whitehead Institute for Biomedical Research/MIT, 9 Cambridge Center, Cambridge, 02142, Massachusetts, USA

    Kevin J. Verstrepen & Gerald R. Fink

  2. Department of Microbiology, University of Tennessee, Knoxville, 37996, Tennessee, USA

    Todd B. Reynolds

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Correspondence to Gerald R. Fink.

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Related links

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DATABASES

SwissProt

ALS1

FLO1

FLO5

FLO9

Sir3

Sup35

FURTHER INFORMATION

Sequencing of Candida albicans at the Stanford Genome Technology Center

Saccharomyces genome database

Glossary

TELOMERES

The physical ends of linear chromosomes. They are associated with specialized nucleoprotein complexes that are required for the protection, replication and stabilization of the chromosome ends. In most organisms, telomeres contain many tandemly repeated DNA sequences called 'terminal repeats'.

SUBTELOMERIC REGIONS

DNA sequences close to telomeres. Genes in these regions are often found in multiple copies on different chromosomes and might be subjected to common regulatory mechanisms as a consequence of their proximity to the telomeres.

UNEQUAL CROSSOVER

A recombination event between DNA sequences that are not correctly aligned. This often occurs in repetitive sequences when the repeat units (DNA motifs) are paired out of register.

MINISATELLITES

Also known as variable-number tandem repeats. These are DNA sequences of variable length that consist of many tandemly repeated DNA motifs of 5–35 base pairs. Minisatellite regions are unstable and often expand or contract during meiosis and mitosis, making them good targets for genotyping.

PSEUDOHYPHAL GROWTH

A form of cell division that results in a filament of elongated cells. The pseudohyphal filament differs from a hypha because each member of the pseudohyphal filament is a distinct cell, whereas the hypha is a long, multi-nucleate filament without separate cells.

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Verstrepen, K., Reynolds, T. & Fink, G. Origins of variation in the fungal cell surface. Nat Rev Microbiol 2, 533–540 (2004). https://doi.org/10.1038/nrmicro927

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