Infection with the fungus Cryptococcus neoformans can cause meningitis (inflammation of the membranes surrounding the brain) and encephalitis (inflammation of the brain itself), conditions that are often lethal. To elicit these effects, the fungus must somehow leave the blood stream and enter the brain, but little is known about how it does this.
A team of researchers, at the University of Calgary, Canada, has now used a form of microscopy known as intravital microscopy, which enables researchers to observe events in real-time in live animals, to visualize in mice the process of brain invasion by Cryptococcus neoformans.
A key observation of the team, led by Christopher Mody, was that Cryptococcus neoformans stops suddenly in mouse brain capillaries that are similar or smaller in diameter than it is. Only after stopping abruptly was the fungus seen to cross the wall of the blood vessel and enter the brain. Interestingly, the protein urease was required for Cryptococcus neoformans to invade the brain, and treatment with a urease inhibitor reduced brain infection. The authors therefore suggest that therapeutics that inhibit urease might help prevent meningitis and encephalitis caused by infection with Cryptococcus neoformans.
In an accompanying commentary, Arturo Casadevall, at Albert Einstein College of Medicine, New York, suggests that such inhibitors might not be applicable in the clinic, because most patients already have substantial brain infection when they first seek medical help. However, he highlights that the study opens up numerous new avenues of research that could be exploited in the clinic in the future.
The research appears in the Journal of Clinical Investigation.
- Meiqing Shi, Shu Shun Li, Chunfu Zheng, Gareth J. Jones, Kwang Sik Kim, Hong Zhou, Paul Kubes and Christopher H. Mody. Real-time imaging of trapping and urease-dependent transmigration of Cryptococcus neoformans in mouse brain. Journal of Clinical Investigation, 2010; DOI: 10.1172/JCI41963
- Arturo Casadevall. Cryptococci at the brain gate: break and enter or use a Trojan horse? Journal of Clinical Investigation, 2010; DOI: 10.1172/JCI42949
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