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 Biofilm discovery suggests new way to prevent dangerous infections
23.05.2017 | University of Texas at Austin

nachricht Another reason to exercise: Burning bone fat -- a key to better bone health
19.05.2017 | University of North Carolina Health Care

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 quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

Im Focus: Using graphene to create quantum bits

In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.

In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

Physicists discover mechanism behind granular capillary effect

24.05.2017 | Physics and Astronomy

Measured for the first time: Direction of light waves changed by quantum effect

24.05.2017 | Physics and Astronomy

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>