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 Fast-tracking T cell therapies with immune-mimicking biomaterials
16.01.2018 | Wyss Institute for Biologically Inspired Engineering at Harvard

nachricht Dengue takes low and slow approach to replication
12.01.2018 | Duke University

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: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

Im Focus: A thermometer for the oceans

Measurement of noble gases in Antarctic ice cores

The oceans are the largest global heat reservoir. As a result of man-made global warming, the temperature in the global climate system increases; around 90% of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

White graphene makes ceramics multifunctional

16.01.2018 | Materials Sciences

Breaking bad metals with neutrons

16.01.2018 | Materials Sciences

ISFH-CalTeC is “designated test centre” for the confirmation of solar cell world records

16.01.2018 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>