Scientists show master control gene is crucial for determining fungal cell shape and virulenc

SAN ANTONIO (Dec. 18, 2008) – Candida albicans, the fungus responsible for yeast infections, is the fourth-largest cause of hospital-acquired bloodstream infections in the U.S. and leads to a mortality rate close to almost 35 percent1. In collaboration with Spain’s Universidad de Valencia, researchers at The University of Texas Health Science Center at San Antonio and The University of Texas at San Antonio are learning more about what makes C. albicans so deadly.

Their paper, published in the Dec. 15-19 Online Early Edition of the Proceedings of the National Academy of Sciences, strongly suggests that a particular form of C. albicans is especially important for virulence. Virulence is the ability of a microorganism to kill its host. The scientists also found that a master control gene is critical for determining the fungus’s cell shape and virulence.

C. albicans is extremely common and is usually harmless to its hosts. “While many pathogens (disease-causing agents) are in soil and air, this one is found only in warm-blooded mammals,” said David Kadosh, Ph.D., assistant professor in the Health Science Center Department of Microbiology and Immunology. “We all have it in our bodies — in the gut, vaginal cavity and mouth — but it is usually held at bay by the immune system. When the immune defenses are compromised, however, this fungus can infect other parts of the body. Understanding more about the genes involved in this process will lead us to potential anti-fungal drug targets.”

Ninety percent of AIDS patients have oral C. albicans infections with characteristic sores in the mouth. Cancer patients, organ transplant patients, and recipients of artificial joints and devices also are at high risk for C. albicans complications, including bloodstream infections.

Typical C. albicans infections have a mixture of the three forms of the fungus. These are called yeast, pseudohyphae and hyphae. C. albicans yeast are oval, budding cells; pseudohyphal cells are elliptical and are connected; and hyphal cells are straight with parallel sides and are connected. “This study, which documents experiments conducted in a mouse model of C. albicans bloodstream infections, shows that, of these three forms, the hyphal form is especially important for virulence,” Dr. Kadosh said.

The investigators shifted the C. albicans mixture more toward the hyphal form in one group of mice but not in the control group. Nearly all the mice with the greater proportion of hyphae died within 11 days. By contrast, most of the mice with fewer hyphae were alive after 30 days.

Interestingly, the researchers found that when the master control gene, called UME6, was expressed at low levels, the cells grew mostly in the pseudohyphal form. By contrast, when the gene was expressed at very high levels, the cells grew completely in the hyphal form. It appeared that both outcomes were determined by increased expression of overlapping sets of target genes. “This suggests that Candida morphologies (changes in shape) are controlled by a common genetic mechanism in a dosage-dependent manner,” Dr. Kadosh said.

The Health Science Center researchers conceived the study and approached the UTSA laboratory of biology professor José López-Ribót, Pharm.D., Ph.D., to perform the mouse studies. “Dr. López-Ribót and I are collaborators in the San Antonio Center for Medical Mycology, which includes at least 15 senior-level scientists at the Health Science Center, UTSA and the UT Austin College of Pharmacy,” Dr. Kadosh said. “This center for medical mycology is one of the largest centers of its type in the country and is well known outside San Antonio.” Mycology is the study of fungi.

 

 

 
The University of Texas Health Science Center at San Antonio is the leading research institution in South Texas and one of the major health sciences universities in the world. With an operating budget of $668 million, the Health Science Center is the chief catalyst for the $15.3 billion biosciences and health care sector in San Antonio’s economy. The Health Science Center has had an estimated $35 billion impact on the region since inception and has expanded to six campuses in San Antonio, Laredo, Harlingen and Edinburg. More than 23,000 graduates (physicians, dentists, nurses, scientists and other health professionals) serve in their fields, including many in Texas. Health Science Center faculty are international leaders in cancer, cardiovascular disease, diabetes, aging, stroke prevention, kidney disease, orthopaedics, research imaging, transplant surgery, psychiatry and clinical neurosciences, pain management, genetics, nursing, dentistry and many other fields. For more information, visit www.uthscsa.edu.

About The University of Texas at San Antonio
The University of Texas at San Antonio is one of the fastest growing higher education institutions in Texas and the second largest of nine academic universities and six health institutions in the UT System. As a multicultural institution of access and excellence, UTSA aims to be a premier public research university providing access to educational excellence and preparing citizen leaders for the global environment.

UTSA serves more than 28,500 students in 64 bachelor’s, 46 master’s and 21 doctoral degree programs in the colleges of Architecture, Business, Education and Human Development, Engineering, Honors, Liberal and Fine Arts, Public Policy, Sciences and Graduate School. Founded in 1969, UTSA is an intellectual and creative resource center and a socioeconomic development catalyst for Texas and beyond.

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1Edmond MB, et al. (1999) Nosocomial bloodstream infections in United States hospitals: A three-year analysis. Clin Infect Dis 29:239-244



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