Discovering the shared protein complex of fungi and mammalian cells

Research performed in Dr Özgür Bayram’s Fungal Genetics and Secondary Metabolism (FGSM) laboratory in Maynooth University has resulted in the discovery and characterisation of a protein complex made from seven proteins, all of which are shared by fungi and mammalian cells.

The results of the study by Dr Nadia Elramli, Dr Betim Karahoda, Dr Özlem Sarikaya-Bayram, and Dean Frawley and colleagues of Maynooth University’s Department of Biology have been published in one of the leading prestigious genetics journals, PLOS GENETICS.

The study has been funded by a Science Foundation Ireland (SFI) Career Development Award.

Dr Özgür Bayram said: “Our findings strongly suggest that fungal and mammalian immunity use similar protein molecules to control their immune defence mechanisms.”

Overall, this work has highlighted the influence of the STRIPAK complex in fungal cell signalling, growth and secondary metabolite production, which may help researchers understand and potentially control similar metabolite production in other fungi.

Dr Özgür Bayram explains: “The next steps of this work involve the application of this knowledge to other more relevant filamentous fungal species, such as Aspergillus flavus and Aspergillus fumigatus.”
“Aspergillus flavus produces dangerous compounds like aflatoxins which cause crop contamination and liver carcinomas, while Aspergillus fumigatus produces toxins such as gliotoxin, which can result in lethal infections in immunocompromised individuals.”

Developing strategies to reduce risks of plant and human infections

Dr Bayram continued: “Future work will aid in characterising the proteins and methods of signalling utilised in these fungi to promote reproduction and secondary metabolite production, which will contribute to developing strategies for reducing the risks of plant and human infections.

“Future work will also show us whether these similar proteins between fungi and mammals play important roles during fungal infections by lowering the mammalian immune system.”

The protein complex discovered by the team, known as the striatin-interacting phosphatase and kinase (STRIPAK) complex, was shown to be critical for fungal growth, development and secondary metabolite production in the mold Aspergillus nidulans. Fungi produce secondary metabolites such as antibiotics, mycotoxins, anticancer compounds and insecticides which exhibit strong bioactive properties against other organisms.

These metabolites such as antibiotics help fungi defend themselves against soil bacteria whereas mycotoxins protect fungi against fungivore predators such as insects, worms and protozoans. Therefore, fungal secondary metabolites are regarded as fungal immune defence molecules or repellents, which are similar to antibody responses of mammalian cells secreted in response to bacterial, viral and fungal pathogens in order to inactivate these pathogens.

The STRIPAK complex is conserved among eukaryotic organisms including fungi and mammals. It controls many cellular processes such as development, cellular transport, signal transduction, stem cell differentiation and cardiac functions.

One of the STRIPAK complex components, known as SIKE in mammalian cells is involved in the modulation of viral defences. Elramli and colleagues showed that the same component (SIKE-like protein) in the fungus Aspergillus nidulans controls the production of the mycotoxin sterigmatocystin which is a defence molecule against fungivore organisms.

In a previous study published in PLOS BIOLOGY in which Dr Bayram was involved, it was shown that velvet family proteins which regulate sterigmatocystin production in this fungus show similarity to mammalian NF-KB proteins which control innate immunity.