Medical Research Council and University of Exeter

Our Research

The Fungal Surface

Similar to plants and bacteria but unlike the cells of animals, the surface of all fungal cells is defined by an outer cell wall that completely covers the underlying cell membrane.

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It gives the cell its shape and acts a protective layer that means that fungi are resistant to many toxic chemicals, enzymes and viruses in the environment. Although the wall is tough, it is also elastic and malleable, enabling the cell to swell and shrink and to be sculpted into all the characteristic spherical and tubular shapes that make up the fungal kingdom of organisms.

Photo credit

Mark Stappers.
Mixed colony of the fungus Aspergillus fumigatus with normal fungal producing green spores on the right and a white fungal mutant on the left, that lacks the ability to produce the pigment melanin.

The fungal wall is essential for life and is unusual as none of its component parts are found in human cells. The fact that fungal cells and human cells are otherwise very similar makes treating fungal infections harder because treatments that are toxic to fungi are also toxic to humans. This makes the cell wall an important target for new drugs as drugs that attack the assembly of the wall have the potential to make highly specific, non-toxic and effective antibiotics. By recognising fungal cell wall signals, the immune system can stimulate an appropriate and specific antifungal immune response.

Photo credit

Tina Bedekovic.
Micrograph of the fungus Candida albicans taken with a super-resolution confocal laser microscope. Thanks to a fluorescent dye named Calcofluor White we can observe and study the features around the surface of this fungus. Bright circles represent scars where daughter cells have separated from mother cells after cell division.

Staff at the MRC-CMM are investigating, in detail, fungal cell wall structure, biochemistry, molecular biology and immunology.

Our work has defined new targets for the creation of new classes or antifungal drugs and has described how the wall is assembled and modified as the fungus grows in the human body and responds to challenge by antibiotics and immune attack.

Photo credit

Carolina Coelho.
Cryptococcus neoformans cells. The cells of the C. neoformans fungus are characteristically round but are irregular in size. The different sized-cells have different functions when this fungus causes disease- we are trying to investigate exactly what those functions are (Mukaremera and Ballou groups). 

We have also discovered new mechanisms by which the immune system recognises specific components of the fungal cell wall and how the fungus tries to disguise itself from the immune system by modifying its wall structure whilst growing in the body.

Photo credit

Carolina Coelho.
Cryptococcus neoformans has a unique characteristic: outside of the cell wall, there is an additional external layer, the ‘capsule’. This layer is made of different sugars than the cell wall; this sugar coating functions as a kind of ‘invisibility cloak’, as it is harder for the human body to detect and bind to this ‘cloak’, enabling this fungal pathogen to cause infection.

In this image, the capsule is seen as a clear halo against a dark background created by India ink (the same ink we use for drawing). The cell wall is marked with faint blue-cyan colour. Note the abundant buds – like in flowers and plants, these are 'daughter cells' growing from a mother. The capsule is present, but invisible, in the previous image.

Text credit

Neil Gow