Virulence Factor That Induces Fatal Candida Infection Identified

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Virulence Factor That Induces Fatal Candida Infection Identified

Science Daily*

http://www.sciencedaily.com/releases/2008/07/080717101104.htm

ScienceDaily (July 17, 2008) — Scientists here have found that

certain substances from bacteria living in the human intestine cause

the normally harmless Candida albicans fungus to become highly

infectious.

This discovery by researchers at Singapore's Agency for Science,

Technology and Research (A*STAR)'s Institute of Molecular and Cell

Biology (IMCB) could possibly lead to the development of novel

treatments for immunocompromised patients infected by the fungus.

The team of scientists, led by Associate Professor Wang Yue, a

principal investigator at the IMCB, identified peptidoglycan (PGN) --

a carbohydrate from bacteria -- as a factor responsible for causing

the conversion of the otherwise harmless C. albicans to its

infectious form.

Once in the infectious form, the fungus is able to invade

surrounding tissues and escape destruction by the body's own immune

cells. Since immunocompromised patients such as those with AIDS or

those undergoing chemotherapy or radiation treatment are extremely

susceptible to fungal-induced systemic infections, this finding

offers an important clue to the basis of C. albicans infections.

After confirming the presence of PGN-derived molecules in human

blood, the researchers discovered that the fungus is able to " sense "

the presence of the same molecules, which are produced in abundance

by bacteria residing in the gastrointestinal track. Earlier studies

suggested that PGNs can enter the blood stream through the

intestinal wall.

When direct binding of the PGN-derived molecules to a specific

protein in C. albicans takes place, it triggers interactions

and " sensing " processes that induce the fungus to start growing

long, threadlike tubes called hyphae, hence signifying its

conversion to the virulent, life-threatening form.

This is the first time that the identities of the " inducer " and that

of its " sensor " in C. albicans have been clearly established.

Said Wang, who has been working on C. albicans for more than eight

years, " It has been more than 50 years since human blood was first

found to contain molecules that can strongly induce C. albicans

infection. In spite of efforts by many laboratories worldwide, the

identity of the 'inducer' remained elusive.

Thus, we are very excited about being able to help solve this long-

held mystery. Finding the PGN sensor in C. albicans is also of great

importance, because we can now develop anti-Candida therapies by

blocking the sensory mechanism. "

According to UNAIDS statistics, the AIDS pandemic claimed an

estimated 2.1 million lives in 2007 alone. The latest findings by

the Singapore researchers may provide insight for the development of

potential anti-Candida therapy in patients suffering from fungal-

induced systemic infections.

Previous research breakthroughs by the IMCB team included the

discovery of the gene involved in triggering the infectious form of

C. albicans, as well as the way in which the gene and its by-

products facilitated the transformation process of the fungus.

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Journal reference:

.. Bacterial Peptidoglycan triggers Candida albicans hyphal growth by

directly activating the adenylyl cyclase Cyr1p. Cell Host & Microbe,

July 17, 2008

Adapted from materials provided by Agency for Science, Technology

and Research (A*STAR), Singapore.

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(2008, July 17). Virulence Factor That Induces Fatal Candida

Infection Identified. ScienceDaily. Retrieved July 17, 2008, from

http://www.sciencedaily.com­ /releases/2008/07/080717101104.htm