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Genetic Links To Fungal Infection Risk Identified

Date:
October 30, 2009
Source:
University College London
Summary:
Two genetic mutations that may put individuals at increased risk of fungal infections have been identified by scientists, increasing understanding about the genetic basis of these infections and potentially aiding the development of new treatments.

Two genetic mutations that may put individuals at increased risk of fungal infections have been identified by scientists from UCL and Radboud University, increasing understanding about the genetic basis of these infections and potentially aiding the development of new treatments.

The two separate studies, published in the New England Journal of Medicine, mark a significant step in the understanding of genetic susceptibility to fungal diseases. The findings have implications for people suffering from chronic mucocutaneous candidiasis (CMC), as well as more common infections like vaginal candidosis (thrush).

The UCL-led research focused on patients from multiple generations of a large family who had suffered from serious recurrent fungal infections that proved lethal in some of those affected. DNA sequencing and genetic mapping techniques enabled the researchers to identify that this family had a recurrent mutation in a gene called CARD9. The team from Radboud University in the Netherlands discovered that a mutation in the gene Dectin-1 is associated with increased susceptibility to vaginal infections by fungi (primarily of the genus Candida).

When these two genes are working correctly, Dectin-1 senses the presence of fungi and prompts the immune cells to send signals that result in CARD9 setting off a molecular response in the immune system to protect against these microorganisms. If Dectin-1 or CARD9 are mutated or missing, the immune system struggles to control Candida and may allow local or even systemic (affecting the entire body) infections to develop.

Both studies involved researchers from across the world. Critical experiments to prove the causality of the CARD9 mutation were done at the Technical University of Munich, Germany, where mice lacking the corresponding gene had been shown to be susceptible to fungal infections. Similarly, demonstration of the molecular mechanisms leading to the loss of fungi recognition by mutated Dectin-1 in mice had been performed by the University of Aberdeen.

Professor Mihai Netea, who led the team from Radboud University, said: "Although the process of host response to fungal infection has previously been studied in mice, it is very interesting to see that it is the same in humans. 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."

Corresponding author Professor Bodo Grimbacher, UCL Infection & Immunity and Consultant Immunologist at The Royal Free Hospital, said: "This discovery enables further insights in the interaction between fungi and the human immune system and may pave the way for future therapeutic options in patients suffering from Candida infections."

Both studies accessed a variety of biological database resources at the National Center for Biotechnology Information (NCBI), 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 UCL paper, helped identify CARD9 as the mutated gene.


Story Source:

The above story is based on materials provided by University College London. Note: Materials may be edited for content and length.


Journal References:

  1. Glocker et al. A Homozygous CARD9 Mutation in a Family with Susceptibility to Fungal Infections. New England Journal of Medicine, 2009; 361 (18): 1727 DOI: 10.1056/NEJMoa0810719
  2. Ferwerda et al. Human Dectin-1 Deficiency and Mucocutaneous Fungal Infections. New England Journal of Medicine, 2009; 361 (18): 1760 DOI: 10.1056/NEJMoa0901053

Cite This Page:

University College London. "Genetic Links To Fungal Infection Risk Identified." ScienceDaily. ScienceDaily, 30 October 2009. <www.sciencedaily.com/releases/2009/10/091028192611.htm>.
University College London. (2009, October 30). Genetic Links To Fungal Infection Risk Identified. ScienceDaily. Retrieved July 28, 2014 from www.sciencedaily.com/releases/2009/10/091028192611.htm
University College London. "Genetic Links To Fungal Infection Risk Identified." ScienceDaily. www.sciencedaily.com/releases/2009/10/091028192611.htm (accessed July 28, 2014).

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