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A resistance mechanism is discovered in a fungus capable of causing 90% mortality

University of the Basque Country News Jun 22, 2017

The study by the Fungal and Bacterial Biomics research group of the UPV/EHU–University of the Basque Country was published in the PLOS ONE journal.

The UPV/EHU's Fungal and Bacterial Biomics research group has established the existence of a new, hitherto unknown resistance mechanism in the fungus Lomentospora prolificans (L. prolificans). This microorganism is multiresistant to the currently used antifungal drugs and leads to between 80% and 100% mortality in patients with weakened immune systems. This study will therefore enable more effective drugs to combat this fungus to be designed.

The research was led by the lecturers Fernando L. Hernando, Aitor Rementeria and Andoni Ramirez and had the participation of the researchers Aize Pellón (whose PhD thesis prompted this piece of work), Idoia Buldain, Xabier Guruceaga, and Aitziber Antoran. The title is "Molecular and cellular responses of the pathogenic fungus Lomentospora prolificans to the antifungal drug voriconazole."

The microorganism L. prolificans (previously known as Scedosporium prolificans) is a filamentous fungus belonging to the group commonly known as moulds, some of which can be seen growing on rotting food (fruit, bread, etc.). And they are distinct from single–celled yeasts, such as Candida albicans or Saccharomyces cerevisiae, which are significant in clinical practice and in the food industry, respectively. The fungus L. prolificans is also common and fairly routinely found in city soils and on industrial estates. Contact with it does not usually cause ailments in healthy individuals thanks to their immunological systems.

However, as Andoni Ramirez, one of the authors of the article, explained, it causes "very serious infections" in patients with an underlying disease such as "cystic fibrosis" or with "weakened immunological systems", as in the case of patients undergoing chemotherapy to treat some kind of cancer, patients who have undergone an organ transplant, or who are suffering Acquired Immune Deficiency Syndrome (AIDS) due to HIV.

This fungus, according to the research, displays great resistance to the most common antifungal drugs such as voriconazol, which is one of the "drugs of choice for treating" infections caused by filamentous fungi. "This work is hugely significant because it establishes the existence of a new resistance mechanism that has so far remained unknown in fungi. We spotted a significant change in the cell wall in response to the antifungal drug voriconazol, which is used preferentially to combat this fungus and other fungal species. These changes take place in the size and composition of its cell wall," he explained.

So this work constitutes the first description of these responses as a defence mechanism against an antifungal drug, thus opening up a new field of possibilities with a view to designing new molecules that will enable this and other fungal infections to be treated more effectively. "Unlike what happens with antibacterial agents, the variety of antifungal compounds is very limited and they function with few mechanisms for acting differently. So should resistant strains or species emerge, the options available to hospitals often tend to be very limited. So the discovery of new resistance mechanisms could firstly increase the number of targets for directing drugs towards; and secondly, explain the intrinsic as well as acquired resistance in other species of pathogenic fungi," he pointed out.
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