Virulence Factor That Induces Fatal Fungal Infection Identified By Singapore Scientists

Main Category: Infectious Diseases / Bacteria / Viruses
Also Included In: GastroIntestinal / Gastroenterology;  Biology / Biochemistry
Article Date: 18 Jul 2008 - 0:00 PDT

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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.

The research findings described in the press release can be found in the July 17, 2008 print issue of Cell Host & Microbe. The paper is titled, "Bacterial Peptidoglycan triggers Candida albicans hyphal growth by directly activating the adenylyl cyclase Cyr1p."

IMCB:

The Institute of Molecular and Cell Biology (IMCB) is a member of Singapore's Agency for Science, Technology and Research (A*STAR) and is funded through A*STAR's Biomedical Research Council (BMRC). It is a world-class research institute that focuses its activities on six major fields: Cell Biology, Developmental Biology, Structural Biology, Infectious Diseases, Cancer Biology and Translational Research,with core strengths in cell cycling, cell signalling, cell death, cell motility and protein trafficking. Its recent achievements include leading an international consortium that successfully sequenced the entire pufferfish (Fugu) genome. The IMCB was awarded the Nikkei Prize 2000 for Technological Innovation in recognition of its growth into a leading international research centre and its collaboration with industry and research institutes worldwide. Established in 1987, the Institute currently has 35 independent research groups with more than 400 staff members. http://www.imcb.a-star.edu.sg

A*STAR:

The Agency for Science, Technology and Research, or A*STAR, is Singapore's lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based Singapore. A*STAR actively nurtures public sector research and development in Biomedical Sciences, Physical Sciences and Engineering, with a particular focus on fields essential to Singapore's manufacturing industry and new growth industries. It oversees 14 research institutes and supports extramural research with the universities, hospital research centres and other local and international partners. At the heart of this knowledge-intensive work is human capital. Top local and international scientific talent drive knowledge creation at A*STAR research institutes. The Agency also sends scholars for undergraduate, graduate and post-doctoral training in the best universities, a reflection of the high priority A*STAR places on nurturing the next generation of scientific talent. http://www.a-star.edu.sg