Efficient Consumption Of Copper Allows Fungus To Infect The Brain

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 individual’s risk of developing meningoencephalitis.