Scientists at Case Western Reserve School of Medicine and University Hospitals (UH) Case Medical Center have discovered how the beneficial fungal yeast, Pichia, holds at bay a harmful fungal yeast, Candida. Candida is the culprit in oral candidiasis, a painful mouth infection known as thrush. The hope for this finding is that components in Pichia could one day become therapeutic agents to stave off not only thrush, but also other life-threatening systemic fungal infections. Research findings about the effect of oral Pichia on Candida appear in the March 13 edition of PLOS Pathogens.
“Our aim was to try to understand what microorganisms live in our mouths. A disturbed equilibrium of these microorganisms can lead to disease,” said the study’s senior author Mahmoud A. Ghannoum, PhD, EMBA, professor of dermatology and pathology at the School of Medicine and director of the Center for Medical Mycology at UH Case Medical Center.
The study involved testing the mouths of 24 patients from UH Case Medical Center — 12 HIV infected and 12 not infected with HIV. HIV-infected patients were selected for comparison in the study because thrush is a common occurrence for them. The oral cavity was tested for fungi and bacteria using pyrosequencing, a method that uses DNA analysis, which is more powerful with greater specificity than conventional, culture-based approaches.
“When we looked at the data, we found to our surprise that bacteria did not change much between HIV-infected patients and those who were not,” Ghannoum said. “However, what changed significantly between the two groups was the composition of the fungal community. We found that when Candida is present, Pichia is not, and when Pichia is present, Candida is not — indicating Pichiaplays an important role in treating thrush.”
From these observations, investigators conducted in vitro (test tube) experiments on Candida and Pichia. When they grew Candida in the test tube in the presence of Pichia, there was a striking reduction in Candida growth. They also discovered that Pichia secretes material, or a protein, that controls Candida. This Pichia-secreted material, referred to as supernatant, inhibits biofilm formation, germination and adherence in Candida, factors that mark a microbe’s level of harmfulness.
Investigators then took their findings to the next level with experiments on three groups of Candida-infected mice. One group of mice was treated with Pichia supernatant. The next group was treated with nystatin, a topical treatment for thrush. Still another group received no treatment. The outcome? In the mouths of the Pichia-treated mice, the level of Candida was nearly eradicated, though traces remained. Even the nystatin-treated mice had far more Candida present than the Pichia-treated mice. Additionally, the physical symptoms, such as tongue appearance, improved in the Pichia-treated group.
“One day, not only could this lead to topical treatment for thrush, but it could also lead to a formulation of therapeutics for systemic fungal infections in all immunocompromised patients,” he said. “In addition to patients with HIV, this would also include very young patients and patients with cancer or diabetes.”
As a next step this year, investigators will study Pichia supernatant to identify its components that inhibit Candida and other fungi.
Founded in 1843, Case Western Reserve University School of Medicine is the largest medical research institution in Ohio and is among the nation's top medical schools for research funding from the National Institutes of Health. The School of Medicine is recognized throughout the international medical community for outstanding achievements in teaching. The School's innovative and pioneering Western Reserve2 curriculum interweaves four themes--research and scholarship, clinical mastery, leadership, and civic professionalism--to prepare students for the practice of evidence-based medicine in the rapidly changing health care environment of the 21st century. Nine Nobel Laureates have been affiliated with the School of Medicine.
Annually, the School of Medicine trains more than 800 MD and MD/PhD students and ranks in the top 25 among U.S. research-oriented medical schools as designated by U.S. News & World Report's "Guide to Graduate Education."
The School of Medicine is affiliated with University Hospitals Cleveland Medical Center, MetroHealth Medical Center, the Louis Stokes Cleveland Department of Veterans Affairs Medical Center, and the Cleveland Clinic, with which it established the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in 2002. case.edu/medicine.
About University Hospitals
University Hospitals, the second largest employer in Northeast Ohio, serves the needs of patients through an integrated network of hospitals, outpatient centers and primary care physicians in 16 counties. At the core of our health system is University Hospitals Case Medical Center, one of only 18 hospitals in the country to have been named to U.S. News & World Report’s most exclusive rankings list: the Best Hospitals 2013-14 Honor Roll. The primary affiliate of Case Western Reserve University School of Medicine, UH Case Medical Center is home to some of the most prestigious clinical and research centers of excellence in the nation and the world, including cancer, pediatrics, women's health, orthopaedics and spine, radiology and radiation oncology, neurosurgery and neuroscience, cardiology and cardiovascular surgery, organ transplantation and human genetics. Its main campus includes the internationally celebrated UH Rainbow Babies & Children's Hospital, ranked among the top children’s hospitals in the nation; UH MacDonald Women's Hospital, Ohio's only hospital for women; and UH Seidman Cancer Center, part of the NCI-designated Case Comprehensive Cancer Center at Case Western Reserve University. UH Case Medical Center is the 2012 recipient of the American Hospital Association – McKesson Quest for Quality Prize for its leadership and innovation in quality improvement and safety. For more information, go to www.uhhospitals.org