Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Research provides new leads in the case against drug-resistant biofilms

11.11.2010
Films of bacteria that form around foreign materials in the body can be very difficult to defeat with drugs, but research led by Brown University biologists has identified a couple proteins that play a key role in building these “biofilms.” This pair could prove to be a very important target for developing new antibiotics to fight infections.

When a foreign object such as a catheter enters the body, bacteria may not only invade it but also organize into a slick coating — a biofilm — that is highly resistant to antibiotics. Like sophisticated organized crime rings, biofilms cannot be defeated by a basic approach of conventional means.

Instead doctors and drug developers need sophisticated new intelligence that reveals the key players in the network and how they operate. New research led by biologists at Brown University provides exactly that dossier on some key proteins in the iconic bacterium E. coli.

In a paper published this week in the Journal of Biological Chemistry, the researchers describe a couple of prime suspect genes and the “toxin-antitoxin” protein pair they produce. By analyzing the structure and binding of the proteins in the exquisite detail of atomic-scale X-ray crystallography, the team at Brown and Texas A&M University makes the case that “MqsR” and “MqsA” proteins are important operators worth targeting in hopes of disrupting the formation of biofilms.

“Developing new antibiotics has been very difficult, and they all pretty much target the same few proteins,” said corresponding author Rebecca Page, assistant professor of molecular biology, cell biology and biochemistry at Brown. “Our proteins belong to a family of proteins that have never been investigated for their ability to lead to novel sets of antibiotics. This really provides a new avenue.”

The main role of the combination, or complex, of MqsA and MqsR is that they appear to control the transcription of many genes, including ones that govern the growth of “persister” cells, which provide biofilms with a mesh of antibiotic-resistant constituents. In normal populations, persisters are one in a million. In biofilms, they are one in a hundred.

“The MqsR:MqsA complex not only binds its own genetic promoter, but also binds and regulates the promoters of other genes that are important for biofilm formation,” Page said. “This is the only known toxin-antitoxin system that is capable of doing this.”

An odd bird

The MqsA antitoxin is as unusual as it is influential, Page’s team reports. For one thing, the protein, which resembles a bird with wide flapping wings — Page likens it to a Klingon “Bird of Prey” ship from Star Trek — needs the metal zinc on each wing tip to keep it stable. When it’s bound to its partner toxin and DNA, the antitoxin also keeps a very tight lid on the toxin’s ability to operate on mRNA, squeezing key parts, or active sites, so close together (about 1 billionth of a meter) that the mRNA simply can’t enter.

Because the toxin’s activity is key to the health and welfare of persister and biofilm cells, the properties of the toxin-antitoxin binding that regulate them give rise to some potential drug development strategies, Page said. For most of the time, the toxin is bound by the antitoxin, allowing cells to grow. Under other conditions, the antitoxin is destroyed and the toxin is free to cleave, or disable, mRNA. That shuts off existing persister and biofilm cells from further growth, and instead keeps them in a dormant state well-protected from things like antibiotics. If that cleaving goes on too long, however, the cells will die.

So two approaches for drug development, Page said, might be to find compounds that can either keep the toxin-antitoxin pair associated all the time (so that the toxin is inactive and thus that no cleaving occurs), or keep them separated all the time (so that the toxin is active and cleaving always occurs). The zinc on the antitoxin may also prove to be a target.

The investigation is ongoing, but the word is now out on the street that for MqsA and MqsR, the heat is on.

In addition to Page, the paper’s other authors are graduate student Breann Brown and Associate Professor Wolfgang Peti in Brown’s Department of Molecular Pharmacology, Physiology, and Biotechnology, and Thomas Wood, professor of chemical engineering at Texas A&M.

David Orenstein | EurekAlert!
Further information:
http://www.brown.edu

Further reports about: Brown E. coli MqsA MqsR iconic bacterium E. coli key protein new antibiotics proteins

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

3rd Symposium on Driving Simulation

23.10.2017 | Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

 
Latest News

Taming 'wild' electrons in graphene

23.10.2017 | Physics and Astronomy

Mountain glaciers shrinking across the West

23.10.2017 | Earth Sciences

Scientists track ovarian cancers to site of origin: Fallopian tubes

23.10.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>