Featured Research

from universities, journals, and other organizations

New Class Of Antibiotics Stops Pathogens In Their Genetic Tracks

Date:
October 24, 2003
Source:
Ohio State University
Summary:
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.

COLUMBUS, Ohio – 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.


Story Source:

The above story is based on materials provided by Ohio State University. Note: Materials may be edited for content and length.


Cite This Page:

Ohio State University. "New Class Of Antibiotics Stops Pathogens In Their Genetic Tracks." ScienceDaily. ScienceDaily, 24 October 2003. <www.sciencedaily.com/releases/2003/10/031024064511.htm>.
Ohio State University. (2003, October 24). New Class Of Antibiotics Stops Pathogens In Their Genetic Tracks. ScienceDaily. Retrieved September 23, 2014 from www.sciencedaily.com/releases/2003/10/031024064511.htm
Ohio State University. "New Class Of Antibiotics Stops Pathogens In Their Genetic Tracks." ScienceDaily. www.sciencedaily.com/releases/2003/10/031024064511.htm (accessed September 23, 2014).

Share This



More Health & Medicine News

Tuesday, September 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Costs Keep Mounting

Ebola Costs Keep Mounting

Reuters - Business Video Online (Sep. 23, 2014) The WHO has warned up to 20,000 people could be infected with Ebola over the next few weeks. As Sonia Legg reports, the implications for the West African countries suffering from the disease are huge. Video provided by Reuters
Powered by NewsLook.com
Ebola Cases Could Reach 1.4 Million Within 4 Months

Ebola Cases Could Reach 1.4 Million Within 4 Months

Newsy (Sep. 23, 2014) Health officials warn that without further intervention, the number of Ebola cases in Liberia and Sierra Leone could reach 1.4 million by January. Video provided by Newsy
Powered by NewsLook.com
WHO: Ebola Cases to Triple in Weeks Without Drastic Action

WHO: Ebola Cases to Triple in Weeks Without Drastic Action

AFP (Sep. 23, 2014) The number of Ebola infections will triple to 20,000 by November, soaring by thousands every week if efforts to stop the outbreak are not stepped up radically, the WHO warned in a study on Tuesday. Duration: 01:01 Video provided by AFP
Powered by NewsLook.com
5 Ways Men Can Prevent Most Heart Attacks

5 Ways Men Can Prevent Most Heart Attacks

Newsy (Sep. 23, 2014) No surprise here: A recent study says men can reduce their risk of heart attack by maintaining a healthy lifestyle, which includes daily exercise. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins