Genetic mutations may put individuals at increased risk for fungal infections

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New research has identified two genetic mutations that may put individuals at increased risk for fungal infections. The research focused on patients with severe fungal infections (primarily of the genus Candida), but the findings may also have implications for patients who have more common mild infections.

The research is published in two studies that appear together in the October 29, 2009 issue of The New England Journal of Medicine. The two independent research teams, one led by Prof. Mihai Netea (Radboud University Nijmegen Medical Centre, The Netherlands) and one led by Prof. Bodo Grimbacher (University College London, Royal Free Campus Hampstead, United Kingdom) discovered that mutations in two proteins involved in the pathway responsible for recognition of fungal beta-glucans substantially impaired the immune system's ability to control fungi. Dr. Netea's team discovered the relationship with mutations in the protein Dectin-1, and Dr. Grimbacher's team identified the relationship with mutations in the CARD9 protein.

The new results show that the mechanisms to protect against fungal infections have been largely conserved by evolution between mice and humans, which is not necessarily the case for other microbes. After sensing the presence of Candida by specialised recognition proteins such as Dectin-1, immune cells send signals from their surface to the inside, where CARD9 acts as an adaptor molecule that integrates those signals. CARD9 then initiates several molecular response mechanisms of the innate and adaptive immune system to protect us from those microorganisms. If Dectin-1 or CARD9 are mutated or missing, our immune system struggles to control Candida and may allow local or even systemic infections to develop.

"These findings are a first step in understanding the genetic susceptibility to common and disabling fungal diseases such as onychomycosis and recurrent vulvovaginal candidiasis," said Dr. Bart Ferwerda, Radboud University, who first identified the Dectin-1 mutations in a family suffering from mucocutaneous fungal infections.

Dr. Erik-Oliver Glocker, first author of the CARD9 paper, noted the potential for this research to lead to treatment advances. "This discovery enables further insights in the interaction between fungi and the human immune system and may pave the way for future therapeutical options in patients suffering from Candida infections," he said.

Both studies involved researchers from across the world. Professor Netea's research group specializes, among other things, in how the human immune system defends itself against fungal infections. The Marie-Curie Excellence Research Group, under the guidance of Prof. Grimbacher, has specialised in inborn errors of the human immune system. Both studies made important usage of a variety of biological database resources at the National Center for Biotechnology Information (NCBI), which is part of the National Library of Medicine at the National Institutes of Health (United States). Dr. Alejandro Schaffer, a researcher at NCBI and a co-author on the paper by Dr. Grimbacher's team, helped identify CARD9 as the mutated gene. Critical experiments to prove the causality of the CARD9 mutation were done in the laboratory of Prof. Jurgen Ruland (Technical University of Munich, Germany), where mice lacking the corresponding Card9 gene had been engineered some years before and had been shown to be susceptible to fungal infections. Similarly, demonstration of the molecular mechanisms leading to the loss of beta-glucan recognition by mutated Dectin-1 had been performed earlier in the laboratory of Prof. Gordon Brown (University of Aberdeen, United Kingdom).


  1. sarah sarah United Kingdom says:

    ive read the article on how candida can be genetic , I believe I have a genetic condition, as my mom and nan have it also. Is there any idea on how genetic candida can be treated, as it seems very much harder to treat than normal candida?

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