Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Switching to new anti-bacterial targets: Riboswitches

19.12.2005


The recently emerged field of bacterial riboswitches may be a good hunting ground for effective targets against bacterial infection, according to a report by Yale researchers in the journal Chemistry and Biology.


Early studies to understand the malnutrition disease, beri beri, led to the identification of vitamin B1 (thiamine, inset, top), a nutrient found in brown rice but not polished white rice. The thiamine analog pyrithiamine (inset, bottom) has toxic effects in bacteria, fungi, and mammals - now shown to be caused in part by interactions with thiamine-specific riboswitches. Upper image is Aspergillus oryzae, a fungus that contains the riboswitch and is killed by pyrithiamine.



Riboswitches are RNA elements that control gene expression in essential metabolic pathways. Researchers in the laboratory of Ronald R. Breaker, the Henry Ford II Professor of Molecular, Cellular and Developmental Biology at Yale, showed that a riboswitch controlling vitamin B1 (thiamine) levels is disrupted in the presence of pyrithiamine, a toxic compound related to the vitamin.

Bacteria and fungi fail to grow in pyrithiamine and become resistant by acquiring mutations in their riboswitches. This work, in combination with the recently solved crystal structures of purine riboswitches, opens a path to the directed design of drugs targeting riboswitches for use as antibiotics.


According to the researchers, it is inevitable that bacteria will evolve and that the drugs we use to cure bacterial infections will eventually become ineffective. While it is often possible to alter existing drugs slightly, they suggest that a longer term and more attractive solution is to create entirely new drugs that target bacteria in completely new ways. This approach lengthens the useful clinical lifetime of a drug and makes it possible to tackle resistant ’superbugs’ with combinations of drugs.

The analog, pyrithiamine, was synthesized decades ago to study the then new field of vitamin nutrition. It was quickly found to be toxic but the mechanism was incompletely understood. Breaker and coworkers show that pyrithiamine is metabolized and binds to the riboswitch controlling thiamine.

Co-authors at Yale on the work are Narasimhan Sudarsan, Smadar Cohen-Chalamish, Shingo Nakamura and Gail Mitchell Emilsson. The study was funded by the Defense Advanced Research Projects Agency, National Institutes of Health, and the David and Lucile Packard Foundation.

Breaker, a Howard Hughes Medical Institute Investigator, is co founder of BioRelix, a company pursuing licensing of intellectual property related to riboswitches.

Janet Rettig Emanuel | EurekAlert!
Further information:
http://www.yale.edu

More articles from Life Sciences:

nachricht Flow of cerebrospinal fluid regulates neural stem cell division
22.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Chemists at FAU successfully demonstrate imine hydrogenation with inexpensive main group metal
22.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

Im Focus: Computer-Designed Customized Regenerative Heart Valves

Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.

Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...

Im Focus: Light-induced superconductivity under high pressure

A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.

Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Supersonic waves may help electronics beat the heat

18.05.2018 | Power and Electrical Engineering

Keeping a Close Eye on Ice Loss

18.05.2018 | Information Technology

CrowdWater: An App for Flood Research

18.05.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>