Fighting Fungi

November 30, 2000

Scientists from Howard Hughes Medical Institute in Ann Arbor, Michigan have made a discovery that may help us win the biomedical war against fungal pathogens. As published in Genes & Development, Dr. Martin Schröder and colleagues have uncovered a specific biological program which prevents the development of the pathogenic form of several fungi, and have thus paved the way for the design of new anti-fungal agents. Depending upon nutrient availability, many fungi are able to switch between two different morphological forms: a unicellular yeast form and a multicellular filament form. For a number of medically and agriculturally relevant fungi, the filament form is necessary for pathogenicity.

Ustilago maydis, Cryptococcus neoformans, and Candida albicans may not sound familiar, but the effects of these fungi certainly are. Well known to any farmer, Ustilago maydis is the cause of corn smut disease. Cryptococcus neoformans is responsible for meningitis. Candida albicans, the most prevalent yeast species in the human GI tract, causes vaginal yeast infections, oral thrush, and can invade tissues and produces fatal systemic infections in immunocompromised people. Under nitrogen-poor conditions, each of these fungi switch to filament form and thus become pathogenic. This physiological response to nutrient availability has been well documented. It is only now beginning to be understood.

Schröder and colleagues have discovered that the unfolded protein response (UPR) mediates this morphological response. The UPR is a cellular stress response, conserved from yeast to humans. Normally, proteins are folded into their proper conformations in the endoplasmic reticulum (ER) compartment of a cell. When unfolded or misfolded proteins accumulate in the ER, the UPR is activated to transiently decrease the level of protein production and ensure that proper folding occurs. Schröder and colleagues have demonstrated that an active UPR represses filament formation. Their experimental data demonstrates that only under nitrogen-rich conditions is an essential UPR gene regulator produced, and therefore the UPR active. Thus, the UPR mediates the environmental regulation of pathogenicity.

The discovery that the UPR represses filament formation lends new insight into the developmental design of anti-fungal therapies. Drugs which impair protein folding or otherwise activate the UPR may serve as models in the search for new anti-fungal agents.
-end-


Cold Spring Harbor Laboratory

Related Proteins Articles from Brightsurf:

New understanding of how proteins operate
A ground-breaking discovery by Centenary Institute scientists has provided new understanding as to the nature of proteins and how they exist and operate in the human body.

Finding a handle to bag the right proteins
A method that lights up tags attached to selected proteins can help to purify the proteins from a mixed protein pool.

Designing vaccines from artificial proteins
EPFL scientists have developed a new computational approach to create artificial proteins, which showed promising results in vivo as functional vaccines.

New method to monitor Alzheimer's proteins
IBS-CINAP research team has reported a new method to identify the aggregation state of amyloid beta (Aβ) proteins in solution.

Composing new proteins with artificial intelligence
Scientists have long studied how to improve proteins or design new ones.

Hero proteins are here to save other proteins
Researchers at the University of Tokyo have discovered a new group of proteins, remarkable for their unusual shape and abilities to protect against protein clumps associated with neurodegenerative diseases in lab experiments.

Designer proteins
David Baker, Professor of Biochemistry at the University of Washington to speak at the AAAS 2020 session, 'Synthetic Biology: Digital Design of Living Systems.' Prof.

Gone fishin' -- for proteins
Casting lines into human cells to snag proteins, a team of Montreal researchers has solved a 20-year-old mystery of cell biology.

Coupled proteins
Researchers from Heidelberg University and Sendai University in Japan used new biotechnological methods to study how human cells react to and further process external signals.

Understanding the power of honey through its proteins
Honey is a culinary staple that can be found in kitchens around the world.

Read More: Proteins News and Proteins Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.