Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Candidalysin – the first toxin of Candida albicans

29.04.2016

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?


Candida albicans attached to the oral mucosa as a yeast cell and forms a filamentous hypha. The hypha produces Candidalysin, which has now been discovered by a team of German and British researchers

Holland, Özel, Zakikhany, Hube


A filamentous hypha formed by Candida albicans enters a cell of the oral mucosa. During this invasion it produces the toxin Candidalysin, as shown by an international team of researchers.

Holland, Özel, Zakikhany, Hube

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 CollegeLondon, 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.

But why did it take researchers several decades of intensive investigations to find the crucial molecule? Similar toxic compounds – peptides – have long been known from other microbial pathogens. Here, the trick is that Candida albicans initially produces a much larger molecule – a polypeptide. The gene encoding for this polypeptide has long been known; however, its function remained elusive. Only now, using state-of-the-art analytics and building on recent insights, Naglik, Hube and their colleagues could successfully detect and characterize the small molecule.

They realized that the polypeptide is cut into small pieces inside the fungus by a certain enzyme, but only one of these peptide fragments is the newly discovered toxin Candidalysin. The scientists chose this particular name because the peptide contributes to the destruction – the “lysis” – of the cell. From a harmless precursor, the dangerous toxin is only produced when it is actually required by the pathogen.

The production of this toxin is tightly linked to a morphological switch, which is crucial for disease. Candida albicans grows in two different forms: either as an egg-shaped yeast cell or as a filamentous hyphal form. In the human body, small numbers of yeast cells are harmless and our immune systems realizes that it does not face any (immediate) danger. However, when invasive filaments are formed, they release Candidalysin, and it is the activity of the toxin itself that is recognized, acting as a “red alert” signal. Therefore, the immune system has learned to recognize Candidalysin in order to discriminate between harmless yeasts and invasive, toxin-producing “dangerous” filaments. “This is an excellent example of co-evolution”, says Bernhard Hube, Professor at Friedrich Schiller University Jena and department head at HKI.

“The pathogen generates a toxin to harm its host and the host quickly senses the toxin and initiates countermeasures”. The biological function of the toxin during normal growth, when the fungus lives harmlessly on the mucosa currently remains unknown.

“These ground-breaking results in fungal infection biology clearly show that in addition to copious amounts of tenacity, the most important factor for scientific success is an excellent power of observation”, states Hube. “Every small result and every observation constantly has to be re-evaluated and re-interpreted until the molecular reality becomes visible. The outstanding international collaboration within our team of researchers has been crucial for our success. For the scientists from Leibniz Institutes this is their own special contribution to this year’s Leibniz Anniversary.”

The fungus Candida albicans and its toxin Candidalysin will continue to keep scientists from Jena, Borstel and London asking questions for many years to come. How does the toxin interact with the immune system? Does the toxin also have activity against bacteria and does this have any effects on common habitats such as in the human gut? What role do other genetic components of the fungus play during infection?

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, doi:10.1038/nature17625. www.nature.com/nature/journal/v532/n7597/full/nature17625.html

Weitere Informationen:

http://www.leibniz-hki.de

Dr. Michael Ramm | idw - Informationsdienst Wissenschaft

More articles from Life Sciences:

nachricht Warming ponds could accelerate climate change
21.02.2017 | University of Exeter

nachricht An alternative to opioids? Compound from marine snail is potent pain reliever
21.02.2017 | University of Utah

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Impacts of mass coral die-off on Indian Ocean reefs revealed

21.02.2017 | Earth Sciences

Novel breast tomosynthesis technique reduces screening recall rate

21.02.2017 | Medical Engineering

Use your Voice – and Smart Homes will “LISTEN”

21.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>