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 A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

nachricht CWRU researchers find a chemical solution to shrink digital data storage
22.06.2017 | Case Western Reserve University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

Im Focus: Optoelectronic Inline Measurement – Accurate to the Nanometer

Germany counts high-precision manufacturing processes among its advantages as a location. It’s not just the aerospace and automotive industries that require almost waste-free, high-precision manufacturing to provide an efficient way of testing the shape and orientation tolerances of products. Since current inline measurement technology not yet provides the required accuracy, the Fraunhofer Institute for Laser Technology ILT is collaborating with four renowned industry partners in the INSPIRE project to develop inline sensors with a new accuracy class. Funded by the German Federal Ministry of Education and Research (BMBF), the project is scheduled to run until the end of 2019.

New Manufacturing Technologies for New Products

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

A new technique isolates neuronal activity during memory consolidation

22.06.2017 | Life Sciences

Plant inspiration could lead to flexible electronics

22.06.2017 | Materials Sciences

A rhodium-based catalyst for making organosilicon using less precious metal

22.06.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>