Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New Compound Prevents First Steps of Fungal Infection

14.08.2013
Discovery by WPI and UMass Medical School team reported in Proceedings of National Academy of Sciences

Targeting serious and sometimes deadly fungal infections, a team of researchers at Worcester Polytechnic Institute (WPI) and the University of Massachusetts Medical School (UMMS) has discovered a chemical compound that prevents fungal cells from adhering to surfaces, which, typically, is the first step of the infection process used by the human pathogen Candida albicans (C. albicans).


Right, C. albicans in its ovoid, harmless state; left, the infectious, filamented state.

After screening 30,000 chemical compounds in a series of tests with live C. albicans, the team found one molecule that prevented the yeast from adhering to human cells or to polystyrene, a common plastic used in many medical devices. Named "filastatin" by the researchers, this molecule now emerges as a candidate for new anti-fungal drug development and as a potential protective material to embed on the surfaces of medical devices to prevent fungal infections.

The team, led by co-principal investigators Paul Kaufman, PhD, professor of molecular medicine at UMMS, and Reeta Rao, PhD, associate professor of biology and biotechnology at WPI, reports its findings in the paper "Chemical screening identifies filastatin, a small molecule inhibitor of Candida albicans adhesion, morphogenesis, and pathogenesis," published online in advance of print by the journal Proceedings of the National Academy of Sciences (PNAS).

"In humans, the most widespread fungal pathogen is Candida albicans, which is also one of the most frequent causes of hospital-acquired infections," the authors write. "We conclude that filastatin is not toxic to the human cell line under our assay conditions, but is unique in that it can impair fungal adhesion both to inert surfaces and to cultured human epithelial cells."

Infection by C. albicans causes common chronic illnesses like thrush and vaginitis, which affect millions of people globally each year and are not easily cleared by the handful of anti-fungal drugs now available. While most fungal infections do not cause serious harm, if one spreads to the bloodstream it can be deadly.

Hospitalized patients with catheters or central intravenous lines are at risk as the fungi can grow on those devices and enter the body. Similarly, patients with implanted medical devices like pacemakers or prosthetic hips or knees are also at risk if the implant carries a fungus into the body. Also, people with compromised immune systems are at greater risk for serious fungal infections. Because of the lack of effective drugs against C. albicans and other pathogenic fungi, the mortality rate for systemic fungal infections is between 30 and 50 percent.

Typically, a blood stream infection of C. albicans or a similar pathogen begins with fungal cells attaching to a surface—a catheter, for example, or epithelial cells lining the mouth—to form what is known as a biofilm. Next, the ovoid shaped yeast cells morph into an invasive filamentous form, extending pointed filaments that penetrate and damage surrounding tissues. In the current study, the team found that filastatin curtailed both steps: it largely prevented C. albicans from adhering to various surfaces, and it significantly reduced filamentation (inspiring the name filastatin).

As a next step, the team tested filastatin's impact on C. albicans cells that had grown unfettered in test wells and had already adhered to the polystyrene walls. When the compound was added to the culture mix, it knocked off many of the fungal cells already stuck to the polystyrene. The inhibitory effects of filastatin were further tested on human lung cells, mouse vaginal cells, and live worms (C. elgans) exposed to the fungus to see if it would reduce adhesion and infection. In all cases, the novel small molecule had significant protective effects without showing toxicity to the host tissues.

Research is now focused on teasing out the precise molecular mechanisms filastatin uses to prevent adhesion and filamentation. "We need to find the target of this molecule," Rao said. "We have some good leads, and the fact that we aren’t seeing toxicity with host cells is very encouraging, but there is more work to be done."

Additional studies on filastatin are underway at both WPI and UMMS. "The molecule affects multiple clinically relevant species, so we're pursuing the idea that it provides a powerful probe into what makes these organisms efficient pathogens," Dr. Kaufman said. "In this era of budget gridlock in Washington, our ability to get funding from the Center for Clinical and Translational Research at UMMS to support this work was essential for allowing us to pursue our ideas for novel ways to approach this important class of hospital-acquired infections."

The project was also funded by a grant from a WPI/UMMS pilot program established to promote collaborations between researchers at the universities to advance early stage translational research. "Joint research programs, such as the pilot program between our institutions, are central to WPI's work in the life sciences," said Michael Manning, PhD, associate provost for research ad interim, at WPI. "As this collaboration between Professors Rao and Kaufman demonstrates so well, both institutions can leverage their complementary expertise for the ultimate advancement of scientific discovery and public health."

Terence R. Flotte, MD, UMMS executive deputy chancellor, provost, and dean of the School of Medicine, agreed. "The faculty of UMass Medical School and WPI possess scientific knowledge and expertise in disciplines that complement each other," he said. "The creation of this type of multidisciplinary team collaboration between the two universities allows us to work synergistically to solve problems important for improving human health."

Eileen Mell | EurekAlert!
Further information:
http://www.wpi.edu

More articles from Health and Medicine:

nachricht Investigators may unlock mystery of how staph cells dodge the body's immune system
22.09.2017 | Cedars-Sinai Medical Center

nachricht Monitoring the heart's mitochondria to predict cardiac arrest?
21.09.2017 | Boston Children's Hospital

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: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

Hope to discover sure signs of life on Mars? New research says look for the element vanadium

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>