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 Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory

nachricht Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>