Here
Come the Genes! Possible Genetic Connection to Candida Yeast Infections
PITTSBURGHA
group of researchers led by Carnegie Mellon University Biological
Sciences Professor Aaron Mitchell has identified a novel regulatory
gene network that plays an important role in the spread of common,
and sometimes deadly, yeast infections. The findings, which establish
the role of Zap1 protein in the activation of genes that regulate
the synthesis of biofilm matrix, will be published in the June 16,
2009, issue of PLoS Biology, a peer-reviewed open-access journal
from the Public Library of Science.
Candida
albicans is a fungus, more specifically a yeast, which approximately
80 percent of people have in their gastrointestinal and genitourinary
tract with no ill effects. However, at elevated levels it can cause
non-life threatening conditions like thrush and yeast infections.
A C. albicans infection becomes much more serious, and can be lethal,
in those with compromised immune systems who have an implantable
medical device, such as a pacemaker or artificial joint, or who
use broad-spectrum antibiotics. Approximately 60,000 Americans develop
such invasive C. albicans infections each year.
Central
to such infections is a substance called biofilm matrix. A biofilm
is a population of microbes, in this case C. albicans cells, joined
together to form a sheet of cells. The cells in the biofilm produce
extracellular components such as proteins and sugars, which form
a cement-like substance called matrix. This matrix serves to protect
the cells of the biofilm, preventing drugs and other stressors from
attacking the cells while acting as a glue that holds the cells
together. By doing this, the matrix provides an environment in which
yeast cells in the biofilm can thrive, promoting infection and drug
resistance.
"Biofilms
have a major impact on human health and matrix is such a pivotal
component of biofilms. It is important to understand how the production
of matrix is regulated," Mitchell said.
In
the study published in PLoS, Mitchell and colleagues found that
the zinc-responsive regulatory protein Zap1 prevents the production
of soluble ?-1,3 glucan, a sugar that is a major component of matrix.
They also identified other genes whose expression is controlled
by Zap1, called Zap1 target genes. They found that these genes encode
for two types of enzymes, glucoamylases and alcohol dehydrogenases,
which both govern the production and maturation of matrix components.
"Understanding
this novel regulatory gene network gives us insight into the metabolic
processes that contribute to biofilm formation, and the role the
network plays in infection," Mitchell said. "By better
understanding the mechanisms by which biofilms develop and grow,
we can start to look at targets for combating infection."
According
to Mitchell, the next steps will be to determine the mechanisms
by which Zap1 target genes regulate matrix production. Understanding
and targeting these mechanisms will allow the researchers to develop
therapeutic small molecules that will block biofilm formation and
diagnostic tools that can detect biofilms before infections spread.
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This
study was funded by the National Institutes of Health.
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