Drug Discovery Opinion

Although saprophytic fungi play an essential role in recycling dead and decaying organic material, they can also cause disease in both plants and animals. Plants and animals have evolved defence mechanisms against infection; one of the most important of these is the production of reactive oxygen species (ROS). This means that pathogenic fungi, in turn, need strategies to deal with oxidative stress and researchers at the Virginia Bioinformatics Institute (VBI) at Virginia Tech and Montana State University have discovered a fungal protein that plays a key role in causing disease in plants and animals and which also shields the pathogen from oxidative stress.

The team looked at two different fungal pathogens; Alternaria brassicicola, which causes widespread damage in cultivated brassicas such as cabbage, broccoli and oilseed rape, and Aspergillus fumigatus, which causes severe, and usually fatal, disease in immunocompromised individuals. With increases in the number of immunosuppressed patients – as a result of transplants, cancer treatment or HIV infection – aspergillosis has become the most common mould infection worldwide.

The researchers found that the fungal protein TmpL is essential for infection of host tissues and helps the fungi to regulate oxidative stress responses caused by the presence of ROS produced both by the host in response to infection and by the fungi themselves as signalling molecules involved in physiological responses, development and virulence. The study suggests that TmpL consists of an AMP-binding domain, six transmembrane domains, and a FAD/NAD(P)-binding domain and is localised in the Woronin body, a specialized peroxisomal organelle found in the cells of hyphae in filamentous fungi. Although TmpL-deficient mutants were more sensitive to external oxidative stress and less virulent than wild-type fungi, experiments with mice that are deficient in generating an oxidative burst suggest that the intracellular regulation of reactive oxygen species in the fungus is most likely more important for pathogenesis than resistance to host-derived oxidative stress. The authors hope that their work, which is published in PLoS Pathogens, could lead to the development of efficient and novel therapeutics for both plant and animal fungal disease.

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