IMCB researchers have have
discovered mechanisms of how Candida albicans, a form of yeast, transforms from its
normally benign
Researchers at the Agency for Science,
Technology and Research's (A*STAR) Institute of Molecular and Cell Biology (IMCB) have
discovered new molecular mechanisms that provide a more detailed understanding of how the
normally benign Dr. Jekyll-like fungus known as Candida albicans transforms into a serious
and often life-threatening Mr. Hyde-like form.
C. albicans can cause serious and
potentially life-threatening infections in the mouth, blood and other tissues of people
who are undergoing cancer chemotherapy or radiation treatments, or who have developed AIDS
or other diseases that damage the immunity of the individual.
In two separate papers published this month
in Developmental Cell and last month in the EMBO journal, the team of scientists led by
Associate Professor (A/P) Wang Yue, Principal Investigator at IMCB, have managed to reveal
previously unknown mechanisms which are responsible for causing the infectious phase of C.
albicans.
The fungus starts its 'attack' on a patient
by changing its oval shape into a filamentous form, which has thin, threadlike appendages
emerging from the cell body. A/P Wang's team, who has been studying C. albicans for more
than seven years, was responsible for identifying the master "controller"
protein called Hgc1 in 20041. This "controller" functions like a regulator and
tells the fungus when to start the transformation from the harmless oval shape to the
infectious filamentous form. "One question remained, however - how does it activate
the cellular machineries that determine the fungal cell shape?" said A/P Wang.
A/P Wang's team found the answer to this
question in two proteins called Rga2 and Cdc11. They discovered that they each function
like a switch on two different cellular machineries that normally determines cell shape.
"The master regulator Hgc1 acts like the 'finger' that flips the switches to start
the infection process" said A/P Wang.
"Our findings have uncovered detailed
molecular mechanisms which define how these two proteins interact with the master
'controller' to cause infections. This
has opened new opportunities for us to investigate further into a new range of therapeutic
targets for fungal infections," explained A/P Wang.
In the same issue of Developmental Cell,
the team's work was given an expert mention2 by a leading C. albicans researcher, Dr.
Peter Sudbery, stating its importance in bringing awareness of the cellular processes that
is necessary for C. albicans to transform to its infectious state.
In addition, the new knowledge of the
detailed interaction of these proteins with other cellular machineries has also revealed
critical information on how cells in general determine their shape, a fundamental question
in biology as Rga2 and Cdc11 are also found in nearly all eukaryotic organisms.
Largely due to the AIDS pandemic in the
last 25 years, the once nearly harmless and commensal fungus Candida albicans has become
one of the most prevalent microbial pathogens in AIDS patients, causing life-threatening
infections with high death rate, especially in infected children.
1Hgc1, a novel hypha-specific G1
cyclin-related protein regulates Candida albicans hyphal morphogenesis. EMBO J. 23:
1845-56, 2004.
2Preview by P. Sudbery Morphogenesis of a
Human Fungal Pathogen Requires Septin Phosphorylation. Developmental Cell 13: 315-316
(2007).
