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A genetic toolbox for fungal infections

When it comes to research on infectious diseases, bacteria and viruses get most of the attention. An EU-funded research project has investigated the often ignored pathogenicity of fungi and how evolution is driving its progress.
A genetic toolbox for fungal infections
Fungal infections actually pose a considerable threat to human welfare by infecting crops, sometimes producing noxious toxins. Incidence of fungal diseases in humans is increasing, particularly in those who have a lowered immune system.

One reason for this alarming change is that fungi can readily exchange genetic material and then evolution may select the most able offspring. This feature has been exacerbated by the rise in international trade that increases the gene pool available for the mixing or recombination.

The project 'The genomic basis of emerging fungal pathogenicity' (FUNGI-PATHNCODE) aimed to find out, genetically speaking, why fungi have reached new heights in their ability to infect humans. Apart from identifying a general toolbox for ability to infect, the researchers investigated if there were differences between plant and animal pathogens.

Researchers built phylomes of different fungal species, two pathogenic Candida species, a range of species of Microbotyrum that infect the pink or carnation family, and a group of fungi, one of which is an important pathogen of rice. For each gene, a phylogenetic tree was constructed and the results, a phylome, identified genes shared by all species as well as those that were species-specific only.

Results showed that evolution of pathogenic fungi was due to gene duplication followed by adaptive evolution driven by positive selection. The key to being an effective pathogen is dependent on the host. What's more, adaptive evolution can occur in pathogenic fungi in a relatively short time, a few million years. Not only did these species become pathogenic in this time span but they were able to infect new hosts — i.e. plants, animals and humans.

For Microbotium, rapid evolution for pathogenicity gave rise to host specificity, followed by speciation and the emergence of a new species. Within the new species, slower more conservative evolution then occurred. Protein secretion genes are highly conserved in the rice pathogens, a feature highly important for infection.

The researchers believe that genes essential for human infection lie within the phylomes. The work will continue beyond the bounds of the project and will focus on the importance of regulatory networks in the evolution of pathogenicity as opposed to genes.

An understanding of the genetic basis of development of pathogenicity could identify relevant gene functions important for the rise in importance of fungi in microbial infections. Ultimately, this can lead to the development of drug targets.

Related information

Keywords

Pathogenic fungi, human, infection, gene, phylome, drug target
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