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

More articles from Life Sciences:

nachricht World’s Largest Study on Allergic Rhinitis Reveals new Risk Genes
17.07.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Plant mothers talk to their embryos via the hormone auxin
17.07.2018 | Institute of Science and Technology Austria

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

World’s Largest Study on Allergic Rhinitis Reveals new Risk Genes

17.07.2018 | Life Sciences

Electronic stickers to streamline large-scale 'internet of things'

17.07.2018 | Information Technology

Behavior-influencing policies are critical for mass market success of low carbon vehicles

17.07.2018 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>