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A colony of Candida albicans, the major human fungal pathogen. Image courtesy of Dr. David Kadosh from a paper published in Molecular Biology of the Cell (April 2008).
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SAN ANTONIO (Jan. 13, 2009) – Candida albicans, the major fungus responsible for yeast infections, is also a leading cause of hospital-acquired bloodstream infections in the U.S. Thankfully, researchers at The University of Texas Health Science Center at San Antonio, in collaboration with The University of Texas at San Antonio and Spain’s Universidad de Valencia, are learning more about what makes C. albicans so deadly.

Their paper, published in the Jan. 13 issue of the Proceedings of the National Academy of Sciences, strongly suggests that a particular form of this fungus is especially important for virulence. Virulence is the ability of a microorganism to kill its host, such as an animal or a human. The scientists also found that a master control gene is critical for determining the fungus’s cell shape and virulence.

A commentary by a leader in the field, highlighting the significance and impact of the finding, is in the same issue of the journal.

Fungus can be deadly for those with immune deficiencies
C. albicans is extremely common and is usually harmless to its hosts. “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,” said David Kadosh, Ph.D., assistant professor in the UT Health Science Center Department of Microbiology and Immunology. “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.”

AIDS, cancer and organ transplant patients most at risk
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.

David Kadosh received his Ph.D. in biological chemistry and molecular pharmacology from Harvard in 1998. He joined the UT Health Science Center Department of Microbiology and Immunology in 2006.

Three forms of fungus give clues to virulence
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
  
• 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 fungal 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.

Mouse studies performed at UTSA
The Health Science Center researchers conceived the study and approached UTSA laboratory of biology Professor José López-Ribot, Pharm.D., Ph.D., to perform the mouse studies. “Dr. López-Ribot 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.

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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 $16.3 billion biosciences and health care sector in San Antonio’s economy. The Health Science Center has had an estimated $36 billion impact on the region since inception and has expanded to six campuses in San Antonio, Laredo, Harlingen and Edinburg. More than 25,600 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.