Navigation Links
Discovery may lead to better Candidiasis drug

Oral biologists at the University at Buffalo have shown for the first time how histatin, the naturally occurring antifungal agent in saliva, kills the oral pathogen Candida albicans, the fungus responsible for most HIV-related oral infections.

Researchers led by Mira Edgerton, D.D.S., Ph.D., discovered that histatin binds to a specific membrane protein called TRK1p, which regulates potassium ion flow through the cell membrane of the pathogenic fungus Candida albicans and allows the cell to regulate its volume.

The binding action of histatin acts like a "foot in the door," said Edgerton, UB research associate professor of oral biology in the UB School of Dental Medicine and senior author on the study. "Blocking the channel open allows a lethal unregulated flow of potassium and other essential molecules into, and out of, the cell.

"This is the first identification of a specific target for histatin," she said. "The finding paves the way for eventually developing a better therapeutic drug for candidiasis."

Results of the research were presented today (March 11, 2005) at the International Association on Dental Research General Session being held in Baltimore.

Candidiasis also is known as thrush, a disease characterized by whitish spots and ulcers on the membranes of the mouth, tongue and throat. It affects primarily people with weakened immune systems caused by antibiotics, chemotherapy or by diseases such as AIDS. Thrush also affects many denture wearers.

The condition can be treated with antifungal medication in otherwise healthy people, said Edgerton, but it is difficult to treat in persons with compromised immunity and can be deadly if it infects vital organs.

Researchers were aware that histatin usually can keep Candida albicans in check in persons with enough saliva and a healthy immune system, but they did not know precisely how histatin accomplished this.

"There are many types of naturally occurring p roteins, such as venoms and toxins, that kill cells by creating holes in the cell membrane," said Edgerton, "but we thought that wasn't the case with histatin. We didn't think it acted in the same way. And we wanted to know why it acts on yeast (fungus is a type of yeast) and not on other types of cells."

Through a series of studies, the researchers identified the target-binding protein on Candida albicans by creating mutant strains of the fungus without the target and exposing the mutants to histatin. Results showed that histatin was significantly less active when the suspect target was missing.

Further research indicated that histatin binding to the target protein killed the fungal cells by preventing it from regulating its ions, the positive and negative charged molecules that move into, and out of, cells. Ions regulate electrostatic pressure between the cells' internal and external environments, which, in turn, regulates their volume and water content. Cells that lose their water content without being able to regulate its re-uptake die rapidly, Edgerton said.

"Now that the target for histatin has been identified, we can design a better protein that will be even more effective in binding and holding the channel open, causing even better and more rapid killing of the fungus," said Edgerton.

"In addition, many other pathogenic fungi that cause disease in elderly individuals or AIDS patients also should be able to be killed by histatins or drugs designed to target their potassium channels."


'"/>

Source:University at Buffalo


Related biology news :

1. Fundamental Finding Yields Insight into Stem Cells, Cancer; Opens Door to Drug Discovery
2. Discovery of key proteins shape could lead to improved bacterial pneumonia vaccine
3. UCSD Discovery Shows How Embryonic Stem Cells Perform Quality Control Inspections
4. Discovery Could Lead To Novel Approaches In HIV Treatment
5. Discovery Promises Simpler Therapy for Sickle Cell Disease
6. Protein Discovery Could Unlock The Secret To Better TB Treatment
7. Discovery clarifies role of peptide in biological clock
8. Eliminate Data Analysis Bottlenecks in Drug Discovery
9. Discovery of New Dopamine Action May Yield Alternative Psychiatric Drugs
10. Discovery could be key to bioterrorism defense
11. Discovery of an American salamander where it shouldnt be: Korea
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:11/24/2016)... Cercacor today introduced Ember TM Sport ... non-invasively measure hemoglobin, Oxygen Content, Oxygen Saturation, Perfusion ... in approximately 30 seconds. Smaller than a smartphone, using ... to key data about their bodies to help monitor ... Hemoglobin carries oxygen to muscles. When hemoglobin ...
(Date:11/22/2016)... 2016   MedNet Solutions , an innovative SaaS-based ... clinical research, is pleased to announce that the company ... Life Sciences Awards as "Most Outstanding in eClinical ... year of recognition and growth for MedNet, which has ... iMedNet ™ , MedNet,s flagship ...
(Date:11/19/2016)... DALLAS , Nov. 18, 2016 Securus ... technology solutions for public safety, investigation, corrections and monitoring, ... a smaller competitor, ICSolutions, to have an independent technology ... set, the most modern high tech/sophisticated telephone calling platform, ... tell customers that they do most of what we ...
Breaking Biology News(10 mins):
(Date:12/5/2016)... -- NxGen MDx announced today that it brought its NxGen Informed Prenatal ... able to improve customer service through shortened turnaround times and at the ... CEO of NxGen MDx. ... A decrease in turnaround times by 25% ... opportunities at the Grand Rapid headquarters. The NxGen Informed Prenatal ...
(Date:12/5/2016)... 2016 The U.S. Biotechnology industry ... billion of revenue and some $890 billion of total ... global biopharmaceuticals, and this figure is expected to exceed ... up these four equities for assessment: Northwest Biotherapeutics Inc. ... ACAD ), Acorda Therapeutics Inc. (NASDAQ: ...
(Date:12/4/2016)... DIEGO , Dec. 3, 2016  In five ... of Hematology (ASH) Annual Meeting and Exposition in ... biomedical engineering methods to improve the delivery of life-saving ... These new methods are designed to carry therapies directly ... needed most, which could provide a substantial advantage over ...
(Date:12/2/2016)... 2016 More than $4.3 million was raised last ... DHMD ). The gala was held at the American Museum ... and honored Alan Alda and ... and medicine and the public understanding of science. Since the ... event has raised $40 million for the Laboratory,s research and ...
Breaking Biology Technology: