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Virulence factor that induces fatal Candida infection identified

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21.07.2008

Culprit is factor produced by intestinal bacteria

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.

The research findings were recently published in the current journal Cell Host & Microbe.

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.

Cathy Yarbrough | Source: EurekAlert!
Further information: www.a-star.edu.sg/
www.imcb.a-star.edu.sg

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