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JCI table of contents -- February 8, 2006

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MICROBIOLOGY: Efficient consumption of copper allows fungus to infect the brain

Infection with the fungus Cryptococcus neoformans is a problem for individuals whose immune system is compromised (for example individuals with HIV and individuals who are taking chemotherapeutics to treat cancer). It can cause either cryptococcal pneumonia or, more seriously, meningoencephalitis. In a study that appears online on February 8 in advance of publication in the March print issue of the Journal of Clinical Investigation, researchers from the University of Illinois at Chicago show that in mice, the infecting fungus must be adapted to grow in the presence of low levels of copper if it is to efficiently infect the brain and cause meningoencephalitis.

Peter Williamson and colleagues showed that C. neoformans lacking a protein that is essential for it to take up copper from its environment (Cuf1) are impaired in their ability to infect the brain and cause fatal meningoencephalitis. By contrast, these mutant C. neoformans infect the lung as efficiently as C. neoformans expressing Cuf1. Consistent with this, bacteria expressing high levels of a protein controlled by Cuf1 (Ctr4) were found in the brain of mice and humans infected with C. neoformans. This study indicates that one factor that can limit the growth of C. neoformans in the brain of mice and humans is low levels of copper, but that this is not a factor limiting growth in the lung. The authors therefore suggest that determining the level of Ctr4 expressed by the C. neoformans infecting an individual might help determine that individuals risk of developing meningoencephalitis.

TITLE: Role of a CUF1/CTR4 copper regulatory axis in the virulence of Cryptococcus neoformans

AUTHOR CONTACT:
Peter R. Williamson
University of Illinois at Chicago, Chicago, Illinois, USA.
Phone: (312) 996-6070; Fax: (312) 413
'"/>

Contact: Karen Honey
press_releases@the-jci.org
212-342-4159
Journal of Clinical Investigation
8-Feb-2007


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