Team of German and British scientists discovers tissue-damaging fungal toxin

In a pioneering study, scientists in Jena, Borstel, Aberdeen and London have discovered a toxin in the fungus Candida albicans, which plays a crucial role during human mucosal infection. Their discovery is has now been published in the journal Nature.

Throughout evolution, pathogens have come up with many tricks to infect and damage their hosts: viruses capture whole cells and turn them into factories for their own replication until the cells are exhausted and die. Infectious bacteria produce multiple molecules that can manipulate the host cell’s metabolism or simply destroy it. But what about human pathogenic fungi?

It is well known that certain fungi produce poisons which, if accidentally consumed, can result in sickness or even death. However, up until now, production of host cell-destroying toxins by the microscopic fungi that can infect us has never been shown. For decades, scientists have been looking for the molecules that are directly responsible for tissue damage during the course of fungal diseases. However, they did not find toxins in pathogenic fungi, which directly damages their infected hosts, and distinguishes these dangerous species from their harmless relatives. This is regrettable, since such knowledge would have been of great value for understanding human fungal infections and for taking therapeutic countermeasures.

Hence, the discovery by a German-British team of researchers came as quite a surprise. Microbiologists from Jena, Borstel, Aberdeen and London succeeded for the first time in identifying a real toxin in Candida albicans – a usually harmless gut-dwelling yeast which frequently causes diseases such as thrush. Candidalysin, as the new toxin was called, destroys human cells by forming holes in their membranes. The team of scientists elucidated this mechanism using cells of the oral mucosa as a model. Oral infections with Candida albicans commonly occur in HIV patients, but also in very young and elderly people with weakened immune systems.

The initial impulse for the discovery came from Julian Naglik’s research group at King’s College London, who has been studying how human oral cells respond to fungal infections. The team of Bernhard Hube at the Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute – (HKI) in Jena, Germany, investigated the interactions between fungus and host on a molecular level and demonstrated that Candidalysin actually damages the host cell. In addition, the biophysicist Thomas Gutsmann at the Leibniz-Center for Medicine and Biosciences in Borstel and his group studied the precise interaction between the fungal toxin and the cell membrane. Additional researchers in the UK and the USA also contributed data. The discovery of Candidalysin was made possible by a successful combination of individual expertise.

Original publication
Moyes DL, Wilson D, Richardson JP, Mogavero S, Tang SX, Wernecke J, Höfs S, Gratacap RL, Robbins J, Runglall M, Murciano C, Blagojevic M, Thavaraj S, Förster TM, Hebecker B, Kasper L, Vizcay G, Iancu SI, Kichik N, Häder A, Kurzai O, Luo T, Krüger T, Kniemeyer O, Cota E, Bader O, Wheeler RT, Gutsmann T, Hube B, Naglik JR (2016) Candidalysin is a fungal peptide toxin critical for mucosal infection. Nature 532, 64–68.
www.nature.com/nature/journal/v532/n7597/full/nature17625.html