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 novel socio-ecological approach helps identifying suitable wolf habitats
17.02.2017 | Universität Zürich

nachricht New, ultra-flexible probes form reliable, scar-free integration with the brain
16.02.2017 | University of Texas at Austin

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Switched-on DNA

20.02.2017 | Materials Sciences

Second cause of hidden hearing loss identified

20.02.2017 | Health and Medicine

Prospect for more effective treatment of nerve pain

20.02.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>