Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Antibiotics based on a new principle may defeat MRSA

19.12.2012
Scientists at Karolinska Institutet have presented a new principle for fighting bacterial infections, in other words, a new type of antibiotic, in the FASEB Journal. The new antibiotic mechanism is based on selectively blocking the thioredoxin system in the cells, which is crucial to the growth of certain bacteria. Scientists hope to be able to treat such conditions as stomach ulcers, TB and MRSA.

"Much work remains to be done, but we believe that it will be possible to use this mechanism when, for example, broad-spectrum antibiotics have proved to be inadequate", says Professor Arne Holmgren, leader of the study now being published.

The thioredoxin system is present in all cells and is central to the ability to make new DNA (genetic material). It is also important in protecting the cell from a process known as oxidative stress, which arises when excess oxygen radicals and other oxidizing agents are formed. This may occur, for example, during the attack by white blood cells on bacteria, and it can damage or kill the cell. The most important components of the thioredoxin system are the enzymes thioredoxin and thioredoxin reductase, of which the first (very simplified) is required in the process of creating the building bricks of what is to be new DNA, and the second ensures that the thioredoxin remains active.

In addition to the thioredoxin system, mammals and humans, and some bacteria, have a second, similar biochemical process in the cell that is based on the enzyme glutaredoxin. The thioredoxin system and the glutaredoxin system act as each other's backup. Many bacteria that cause disease, however, such as Helicobacter pylori (which cause stomach ulcers), the TB bacterium Mycobacterium tuberculosis, and the multiresistant staphylococcus bacterium MRSA, have only the thioredoxin system. These bacteria lack the glutaredoxin system. This makes these bacteria very vulnerable to substances that inhibit thioredoxin and thioredoxin reductase.

"Furthermore, the thioredoxin reductases in bacteria are very different in chemical composition and structure from the human enzyme. And it is just these differences, and the fact that certain bacteria lack the glutaredoxin system, that mean that drugs that affect thioredoxin reductase can be used as antibiotics. This is what we have discovered", says Arne Holmgren.

The study now being published describes how the scientists have used a drug candidate known as ebselen, which has previously been tested in the treatment of stroke and inflammation. The scientists discovered that ebselen and similar synthetic substances inhibit, among other things, thioredoxin reductase in bacteria. The scientists saw in laboratory experiments how the ebselen killed certain types of bacteria and not others. They were able to modify the genetic properties of Escherichia coli (E. coli), which is normally not susceptible to ebselen, and in this way investigate the mechanisms behind the antibiotic effect. They showed that the bacteria in which the genes in the DNA molecule that code for the glutaredoxin enzyme or the formation of the tripeptide glutathione, which is another important component of the glutaredoxin system, had been switched off were must more susceptible to ebselen than normal.

Bacteria that are resistant to several different types of antibiotic are a serious and extensive problem all over the world. The method of attacking bacteria by preventing the construction of their cell wall, which was discovered when penicillin was discovered at the beginning of the 20th century, is still used, in several variations. It has for this reason long been obvious that science must find new ways of combating diseases caused by bacterial infections. The scientists who have written the article believe that the new antibiotic principle they are presenting may be a part of the solution.

"It is particularly interesting that MRSA and the antibiotic-resistant TB are also susceptible to ebselen and new synthetic substances. And it's worth noting that ebselen is an antioxidant, just as vitamin C is. This means that it protects the host against oxidative stress, and in this way we can kill two birds with one stone", says Arne Holmgren.

In addition to Arne Holmgren's research group at Karolinska Institutet, scientists at Uppsala University, the Swedish Institute for Communicable Disease Control, and the World Health Organisation (WHO) have taken part in the study. The work has been financed with grants from the Swedish Cancer Society, the Swedish Research Council, Vinnova, the Knut and Alice Wallenberg Foundation and Karolinska Institutet.

Publication:

Jun Lu, Alexios Vlamis-Gardikas, Karuppasamy Kandasamy, Rong Zhao, Tomas N Gustafsson, Lars Engstrand, Sven Hoffner, Lars Engman, Arne Holmgren

Inhibition of bacterial thioredoxin reductase: an antibiotic mechanism targeting bacteria lacking glutathione

FASEB Journal, online 17 December 2012, doi:10.1096/fj.12-223305 , Vol. 27 April 2013

The Press Office | EurekAlert!
Further information:
http://www.ki.se

More articles from Health and Medicine:

nachricht Penn studies find promise for innovations in liquid biopsies
30.03.2017 | University of Pennsylvania School of Medicine

nachricht 'On-off switch' brings researchers a step closer to potential HIV vaccine
30.03.2017 | University of Nebraska-Lincoln

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

NASA laser communications to provide Orion faster connections

30.03.2017 | Physics and Astronomy

Reusable carbon nanotubes could be the water filter of the future, says RIT study

30.03.2017 | Studies and Analyses

Unique genome architectures after fertilisation in single-cell embryos

30.03.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>