Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Urine helps infectious yeast stick

31.03.2005


Researchers from Johns Hopkins and the University of Maryland have discovered that urine actually helps a particular yeast stick to cells along the urinary tract. The finding might offer a new way to prevent or treat certain yeast and fungal infections, and the researchers’ work also provides an unexpected new role for some proteins already known to help hungry yeast live longer.



Writing in the March 18 issue of Science, the researchers report that the yeast Candida glabrata use a family of proteins called sirtuins to block access to genes that would otherwise help the yeast stick. The sirtuins, which also help regulate the organism’s lifespan, require niacin, or vitamin B3, to work. But urine has only tiny amounts of niacin, so the sirtuins don’t work, the genes are exposed, and the yeast can make the proteins that help it stick to cells in the urinary tract, the researchers discovered.

C. glabrata and its cousin C. albicans cause infections in blood and in mucosal tissues such as the urinary tract and vagina. C. glabrata is the second leading cause (behind C. albicans) of yeast infections, or candidiasis, in people with urinary catheters. Unlike some other yeast, C. glabrata can’t make niacin and instead has to import it from its surroundings.


"This particular yeast has in some sense committed to living with the human host and so it takes advantage of us to provide certain key nutrients," says Brendan Cormack, Ph.D., professor of molecular biology and genetics in Johns Hopkins’ Institute for Basic Biomedical Sciences.

"It turns out that there’s enough niacin in blood to keep the yeast’s adhesion-promoting genes turned off, we discovered," he adds. "But in urine and perhaps other host environments, there is such a limited amount of niacin that these genes are turned on, allowing the organism to stick to host cells."

The new study builds on the lab’s discovery in 1999 that C. glabrata sticks to cells that line mucosal tissues and blood vessels thanks to the products of genes dubbed EPAs by Cormack’s team. Then, in 2003, postdoctoral fellows Alejandro De Las Peñas and Irene Castaño discovered that yeast missing the gene for Sir3 were super-sticky.

"Among other things, Sir3 and specific other proteins attach themselves near the tips of chromosomes, obscuring the nearby genes," says Cormack. "It turns out that the yeast’s adhesion-promoting genes are near the chromosome tips and are usually silenced by this process. In yeast missing Sir3, the EPA genes were exposed and used."

The researchers’ latest work demonstrates that environmental influences -- not just the engineered loss of a gene -- can dictate whether the yeast can use these EPA genes. The environment’s effect on these genes helps the organism recognize a good place to colonize, says Cormack.

In the new work, graduate student Renee Domergue studied C. glabrata she had engineered to become permanently drug-resistant if the adhesion-promoting genes got turned on, which would only happen if Sir3 and the other proteins had stopped covering them up for some reason.

No drug resistance developed in blood, but Domergue did detect it in a mouse model of bladder infection that had been developed by collaborator David Johnson of the University of Maryland School of Medicine. Turning to laboratory dishes again, Domergue discovered that the yeast rapidly became drug-resistant (indicating the adhesion-promoting genes had been turned on) when they were grown in artificial urine -- a mix of specific chemicals in known amounts.

"We then tested each of the components of the urine, but none triggered the switch," says Cormack. "So the trigger was actually something that was ’limiting’ in the urine, that is, it was present in only tiny amounts -- the vitamin niacin."

Niacin, also known as nicotinic acid, is used by cells to make an important molecule called NAD+ for short. NAD+ binds to sirtuins and is required for them to work properly. (Johns Hopkins scientist Cynthia Wolberger and colleagues recently showed how this happens.) Without niacin, these yeast can’t make NAD+, and so the sirtuins don’t block access to the EPA genes, the researchers report.

Other researchers have reported that the EPA genes also help C. glabrata stick to plastic, which might explain the organism’s propensity to cause catheter infections.

"We don’t know whether niacin supplements might help prevent these catheter infections, or whether the plastic could be treated somehow to reduce the organism’s ability to bind to it. But there can be significant liver toxicity associated with niacin supplements, so the question would have to be studied very carefully," cautions Cormack.

Not all yeast would be affected by the lack of niacin in the same way, because some, like the popular laboratory yeast S. cerevisiae, can make niacin themselves, and others don’t use sirtuins to regulate their adhesion-promoting genes.

The research was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Allergy and Infectious Disease. Authors on the paper are Domergue, Castaño, De Las Peñas, Cormack and Margaret Zupancic of Johns Hopkins; and Virginia Lockatell, Richard Habel and Johnson of the University of Maryland School of Medicine. Castaño and De Las Peñas are now at the Instituto Potosino de Investigacion Cientifica y Tecnologica, San Luis Potosi, Mexico.

Joanna Downer | EurekAlert!
Further information:
http://www.jhmi.edu
http://www.sciencemag.org

More articles from Health and Medicine:

nachricht Bioinspired nanoscale drug delivery method developed by WSU, PNNL researchers
10.01.2019 | Washington State University

nachricht How herpesviruses shape the immune system
09.01.2019 | German Center for Infection Research

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Flying Optical Cats for Quantum Communication

Dead and alive at the same time? Researchers at the Max Planck Institute of Quantum Optics have implemented Erwin Schrödinger’s paradoxical gedanken experiment employing an entangled atom-light state.

In 1935 Erwin Schrödinger formulated a thought experiment designed to capture the paradoxical nature of quantum physics. The crucial element of this gedanken...

Im Focus: Nanocellulose for novel implants: Ears from the 3D-printer

Cellulose obtained from wood has amazing material properties. Empa researchers are now equipping the biodegradable material with additional functionalities to produce implants for cartilage diseases using 3D printing.

It all starts with an ear. Empa researcher Michael Hausmann removes the object shaped like a human ear from the 3D printer and explains:

Im Focus: Elucidating the Atomic Mechanism of Superlubricity

The phenomenon of so-called superlubricity is known, but so far the explanation at the atomic level has been missing: for example, how does extremely low friction occur in bearings? Researchers from the Fraunhofer Institutes IWM and IWS jointly deciphered a universal mechanism of superlubricity for certain diamond-like carbon layers in combination with organic lubricants. Based on this knowledge, it is now possible to formulate design rules for supra lubricating layer-lubricant combinations. The results are presented in an article in Nature Communications, volume 10.

One of the most important prerequisites for sustainable and environmentally friendly mobility is minimizing friction. Research and industry have been dedicated...

Im Focus: Mission completed – EU partners successfully test new technologies for space robots in Morocco

Just in time for Christmas, a Mars-analogue mission in Morocco, coordinated by the Robotics Innovation Center of the German Research Center for Artificial Intelligence (DFKI) as part of the SRC project FACILITATORS, has been successfully completed. SRC, the Strategic Research Cluster on Space Robotics Technologies, is a program of the European Union to support research and development in space technologies. From mid-November to mid-December 2018, a team of more than 30 scientists from 11 countries tested technologies for future exploration of Mars and Moon in the desert of the Maghreb state.

Close to the border with Algeria, the Erfoud region in Morocco – known to tourists for its impressive sand dunes – offered ideal conditions for the four-week...

Im Focus: Programming light on a chip

Research opens doors in photonic quantum information processing, optical signal processing and microwave photonics

Researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) have developed a new integrated photonics platform that can...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Our digital society in 2040

16.01.2019 | Event News

11th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Aachen, 3-4 April 2019

14.01.2019 | Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

 
Latest News

Velcro for human cells

16.01.2019 | Life Sciences

Kiel physicists discover new effect in the interaction of plasmas with solids

16.01.2019 | Physics and Astronomy

The pace at which the world’s permafrost soils are warming

16.01.2019 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>