Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New class of antibiotics stops pathogens in their genetic tracks

24.10.2003


Researchers have found that a promising new class of antibacterial chemicals inhibits one of the most fundamental processes of life – a cell’s ability to express genetic material. Knowing exactly how these chemicals keep bacterial cells in check can help scientists make more effective antibiotics.

Like many bacterial inhibitors, this new class of compounds – called the CBR703 series – inhibits RNA polymerase, the key enzyme in gene expression. However, the unique mechanism that these compounds use to inhibit RNA polymerase was previously unknown and is first described in this week’s journal Science.

"It’s a long way between knowing that something will kill bacteria and figuring out the exact process by which the bacteria is killed," said Irina Artsimovitch, a study co-author and an assistant professor of microbiology at Ohio State University. "Other antibiotics also inhibit RNA polymerase, but the ones in this study use a radically different inhibitory mechanism."



According to the study, CBR703 inhibitors hindered the ability of RNA polymerase in Escherichia coli to perform crucial catalytic functions, such as building molecules of RNA. Compounds in the CBR703 series – all are synthetic chemicals – render RNA polymerase useless by binding to a specific place on the enzyme – a necessary step in the process.

"Unless you know where the inhibitor binds, you can’t draw any conclusions about how that inhibitor affects its target," Artsimovitch said. "On the other hand, once you have this information, you could predict if the inhibitor would be effective against a broad range of bacteria, as the binding site may not be the same in RNA polymerase enzymes from different bacteria."

She and her colleagues chose to study the effects of CBR703 inhibitors on E. coli, since the RNA polymerase enzyme in many pathogens is similar to that found in the E. coli bacteria. CBR703 compounds are not yet used as commercial antibiotics.

While the CBR703 inhibitors seemed to stop gene expression in E. coli, the researchers found that the compounds wouldn’t inhibit RNA polymerase in human cells. Finding this lack of inhibition from human cells is key to designing new drugs, as some antibiotic compounds could harm both bacteria and human cells.

"When we find something that inhibits a particular process, it’s easier to make targeted drugs," Artsimovitch said. "In this case, finding something that inhibited bacterial RNA polymerase lets us look at the structure of the enzyme and determine how to improve the inhibitors further to make them more effective."

Artsimovitch conducted the study with Robert Landick, a professor of microbiology at the University of Wisconsin-Madison and Clement Chu and A. Simon Lynch, both with Cumbre, Inc., a drug discovery firm in Dallas.

The researchers at Cumbre, Inc., prepared and analyzed a large set of chemical compounds in order to find one that would inhibit transcription in E. coli. Transcription is the first step of gene expression, when a copy of RNA is made from a DNA sequence.

After finding that CBR703 inhibited transcription in E. coli, the researchers ran the bacteria through a series of tests that allowed them to see where and when during transcription the inhibitor acted on the enzyme.

Transcription is a multi-step process in which the genetic information from DNA is transcribed, or written on, RNA. Transcription is key for all cellular processes. In this study, CBR703 inhibited the addition of nucleotides – individual units that make up an RNA molecule – thus keeping a new strand of RNA from forming.

"Knowing how a new antibiotic acts on its target takes the process of making new drugs to a new level, allowing for better understanding of a drug’s direct- and side-effects," she said. This new series of antibacterial compounds holds great promise for designing drugs specifically targeted to major classes of bacterial pathogens, such as those that cause pneumonia and tuberculosis.

"Whenever a new class of antibacterial compounds becomes available, it leads to a surge in enthusiasm in the medical community, since novel antibiotics can provide new treatments, or at least may provide new weapons against pathogenic bacteria that have developed resistance to other drugs," Artsimovitch said.

This research was supported by grants from the National Institutes of Health and the U.S. Department of Agriculture and in part by Cumbre, Inc. Artsimovitch has no link to Cumbre beyond the scope of this study.

Contact: Irina Artsimovitch; +1 (614) 292-6777; Artsimovitch.1@osu.edu

Irina Artsimovitch | Ohio State University
Further information:
http://www.osu.edu

More articles from Life Sciences:

nachricht Toward a 'smart' patch that automatically delivers insulin when needed
18.01.2017 | American Chemical Society

nachricht 127 at one blow...
18.01.2017 | Stiftung Zoologisches Forschungsmuseum Alexander Koenig, Leibniz-Institut für Biodiversität der Tiere

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

A big nano boost for solar cells

18.01.2017 | Power and Electrical Engineering

Glass's off-kilter harmonies

18.01.2017 | Materials Sciences

Toward a 'smart' patch that automatically delivers insulin when needed

18.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>