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 Microscope measures muscle weakness
16.11.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

nachricht Good preparation is half the digestion
16.11.2018 | Max-Planck-Institut für Stoffwechselforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: UNH scientists help provide first-ever views of elusive energy explosion

Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.

Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...

Im Focus: A Chip with Blood Vessels

Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.

Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

Im Focus: Penn engineers develop ultrathin, ultralight 'nanocardboard'

When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure

Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

European Space Talks: Weltraumschrott – eine Gefahr für die Gesellschaft?

23.10.2018 | Event News

 
Latest News

Purdue cancer identity technology makes it easier to find a tumor's 'address'

16.11.2018 | Health and Medicine

Good preparation is half the digestion

16.11.2018 | Life Sciences

Microscope measures muscle weakness

16.11.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>