Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Blockade of pathogen's metabolism

09.04.2013
The search for new antibiotics: Tiny proteins prevent bacterial gene transcription

In the search for new antibiotics, researchers are taking an unusual approach: They are developing peptides, short chains of protein building blocks that effectively inhibit a key enzyme of bacterial metabolism.


Bacteria such as Escherichia coli, shown here in electron microscopic magnification, are susceptible to the novel antibiotic peptides developed by HIPS researchers. © HZI / Rohde

Now, scientists at the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) in Saarbrücken, a branch of the Helmholtz Center for Infection Research (HZI), have published their findings and the implications for potential medical application in the scientific journal ACS Chemical Biology.

The road from gene to protein has an important stop along the way: ribonucleic acid, or RNA. This molecule is essentially a "negative copy" of DNA, the cell's hereditary material, and serves as a blueprint for the cell to make proteins, the basic building blocks of life. This "template" is assembled by the enzyme RNA polymerase, whose job it is to read off the information that is stored within the DNA molecule.

Bacterial RNA polymerase consists of several subunits. The core enzyme has to first bind a certain protein molecule called "sigma factor" which essentially allows the enzyme to begin production of the RNA molecule. The sigma factor locates the starting point of the gene to be copied - as soon as its job is done, it once again detaches from the enzyme complex. The next time, the sigma factor and the core enzyme have to bind to each other again. If this is no longer possible, new RNA cannot be synthesized and no more proteins will be made by the cell. Cellular processes come to a complete standstill, and the bacterium dies.

Which is exactly the reason why the point of contact between the sigma factor and the core enzyme represents a potential target for new therapies against bacterial infections. Another feature makes this a particularly attractive target: "Sigma factors are unique to bacteria and are not found in mammalian cells," explains Kristina Hüsecken, Ph.D. student at the HIPS and the publication's first author. "This way, we are able to specifically target the bacteria without putting the body's own cells at risk." Which also means potential side effects are not to be expected.

The drug researchers from Saarbrücken have looked at a range of peptides, short chains of amino acids, capable of inhibiting the polymerase. Their structure corresponds to areas from the binding site of one of the enzyme parts: A perfect fit, the peptides dock either to the core enzyme or to the sigma factor, specifically at the exact location where the counterpart would normally attach to. This way, the components are prevented from combining to form a functional enzyme since the binding site is already occupied. Of the 16 total peptides the researchers examined, one in particular proved especially effective. The peptide called P07 was able to show in further tests that it actually does prevent transcription of DNA to RNA in bacterial cells by interfering with the interaction between sigma and core enzyme.
A number of current antibiotics target bacterial RNA polymerase, among them rifampicin, which was first introduced in the late 1960s. Yet these classic drugs are quickly losing their efficacy, as germs are evolving resistance to them. "Since we're looking at a new mode of action, it won't come to cross resistance, which is a much-feared issue with new antibiotics," says Dr. Jörg Haupenthal, the study's principal investigator. This could be the case with any new substance whose mode of action is similar to that of an antibiotic the bacteria have already evolved resistance to.

Whether or not P07 will be developed into a market-ready drug is something Haupenthal and his colleagues cannot predict. "Even though our research points the way to new and effective antibiotics, actually developing them into full-blown drugs for clinical use requires much additional research," says Haupenthal. As such, the researchers are working at optimizing P07 while also looking for other molecules capable of binding to the same spot on the polymerase enzyme.

Original publication:
K. Hüsecken, M. Negri, M. Fruth, S. Boettcher, R.W. Hartmann, J. Haupenthal
Peptide-Based Investigation of Escherichia coli RNA Polmerase σ(70):Core Interface As Target Site

ACS Chemical Biology, 2013, DOI: 10.1021/cb3005758 http://dx.doi.org/10.1021/cb3005758

Weitere Informationen:

http://dx.doi.org/10.1021/cb3005758
- Link to the original publication
http://www.helmholtz-hzi.de/en/news_events/news/view/article/complete/
blockade_of_pathogens_metabolism/
- This press release at helmholtz-hzi.de

Dr. Jan Grabowski | Helmholtz-Zentrum
Further information:
http://www.helmholtz-hzi.de

More articles from Life Sciences:

nachricht What the world's tiniest 'monster truck' reveals
23.08.2017 | American Chemical Society

nachricht Treating arthritis with algae
23.08.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

What the world's tiniest 'monster truck' reveals

23.08.2017 | Life Sciences

Treating arthritis with algae

23.08.2017 | Life Sciences

Witnessing turbulent motion in the atmosphere of a distant star

23.08.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>