Featured Research

from universities, journals, and other organizations

Scientists use nature against nature to develop an antibiotic with reduced resistance

Date:
April 10, 2013
Source:
Rockefeller University
Summary:
A new broad range antibiotic has been found to kill a wide range of bacteria, including drug-resistant Staphylococcus (MRSA) bacteria that do not respond to traditional drugs, in mice. The antibiotic, Epimerox, targets weaknesses in bacteria that have long been exploited by viruses that attack them, known as phage, and promises to avoid the problem of resistance that plagues other antibiotics.

A new broad range antibiotic, developed jointly by scientists at The Rockefeller University and Astex Pharmaceuticals, has been found to kill a wide range of bacteria, including drug-resistant Staphylococcus (MRSA) bacteria that do not respond to traditional drugs. The antibiotic, Epimerox, targets weaknesses in bacteria that have long been exploited by viruses that attack them, known as phage, and has even been shown to protect animals from fatal infection by Bacillus anthracis, the bacteria that causes anthrax.

Target selection is critical for the development of new antimicrobial agents. To date, most approaches for target selection have focused on the importance of bacterial survival. However, in addition to survival, the Rockefeller scientists believe that molecular targets should be identified by determining which cellular pathways have a low probability for developing resistance.

"For a billion years, phages repeatedly have infected populations of bacteria, and during this period of time they have identified weaknesses in the bacterial armor," says senior author Vincent A. Fischetti, professor and head of the Laboratory of Bacterial Pathogenesis and Immunology. "We're taking advantage of what phage have 'learned' during this period for us to identify new antibiotic targets that we believe will escape the problem of resistance found for other antibiotics."

The path to identification of this new target spanned more than seven years of effort. Fischetti and his colleagues used a phage-encoded molecule to identify a bacterial target enzyme called 2-epimerase, which is used by Bacillus anthracis to synthesize an essential cell wall structure. In 2008, Fischetti's lab, with Rockefeller's Erec Stebbins and his colleagues in the Laboratory of Structural Microbiology, solved the crystal structure of this enzyme. Based on this work, the researchers identified a previously unknown regulatory mechanism in 2-epimerase that involves direct interaction between one substrate molecule in the enzyme's active site and another in the enzyme's allosteric site. Fischetti and his colleagues chose to target the allosteric site of 2-epimerase to develop inhibitory compounds, because it is found in other bacterial 2-epimerases but not in the human equivalent of the enzyme.

Through the collaboration with Astex, initiated by co-author Allan Goldberg, an inhibitor of 2-epimerase named Epimerox was developed. Raymond Schuch, a former postdoctoral researcher in Fischetti's lab, tested the inhibitor in mice infected with Bacillus anthracis. He found that not only did Epimerox protect the animals from anthrax, but the bacteria did not develop resistance to the inhibitor. The researchers also found that Epimerox was able to kill methicillin-resistant Staphylococcus aureus (or MRSA) with no evidence of resistance even after extensive testing. Their work was published this week in PLOS ONE.

"Since nearly all Gram-positive bacteria contain 2-epimerase, we believe that Epimerox should be an effective broad-range antibiotic agent," says Fischetti. "The long-term evolutionary interaction between phage and bacteria has allowed us to identify targets that bacteria cannot easily change or circumvent. That finding gives us confidence that the probability for developing resistance to Epimerox is rather low, thereby enabling treatment of infections caused by multi-drug-resistant bacteria such as MRSA. It is a very encouraging result at a time when antibiotic resistance is a major health concern."


Story Source:

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


Journal Reference:

  1. Raymond Schuch, Adam J. Pelzek, Assaf Raz, Chad W. Euler, Patricia A. Ryan, Benjamin Y. Winer, Andrew Farnsworth, Shyam S. Bhaskaran, C. Erec Stebbins, Yong Xu, Adrienne Clifford, David J. Bearss, Hariprasad Vankayalapati, Allan R. Goldberg, Vincent A. Fischetti. Use of a Bacteriophage Lysin to Identify a Novel Target for Antimicrobial Development. PLoS ONE, 2013; 8 (4): e60754 DOI: 10.1371/journal.pone.0060754

Cite This Page:

Rockefeller University. "Scientists use nature against nature to develop an antibiotic with reduced resistance." ScienceDaily. ScienceDaily, 10 April 2013. <www.sciencedaily.com/releases/2013/04/130410201828.htm>.
Rockefeller University. (2013, April 10). Scientists use nature against nature to develop an antibiotic with reduced resistance. ScienceDaily. Retrieved April 21, 2014 from www.sciencedaily.com/releases/2013/04/130410201828.htm
Rockefeller University. "Scientists use nature against nature to develop an antibiotic with reduced resistance." ScienceDaily. www.sciencedaily.com/releases/2013/04/130410201828.htm (accessed April 21, 2014).

Share This



More Plants & Animals News

Monday, April 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Breakfast Foods Are Getting Pricier

Breakfast Foods Are Getting Pricier

AP (Apr. 21, 2014) Breakfast is now being served with a side of sticker shock. The cost of morning staples like bacon, coffee and orange juice is on the rise because of global supply problems. (April 21) Video provided by AP
Powered by NewsLook.com
Mich. Boy Unearths 10,000-Year-Old Mastodon Tooth

Mich. Boy Unearths 10,000-Year-Old Mastodon Tooth

Newsy (Apr. 20, 2014) A 9-year-old Michigan boy was exploring a creek when he came across a 10,000-year-old tooth from a prehistoric mastodon. Video provided by Newsy
Powered by NewsLook.com
Vermont Goat Meat Gives Refugees Taste of Home

Vermont Goat Meat Gives Refugees Taste of Home

AP (Apr. 18, 2014) Dairy farmers and ethnic groups in Vermont are both benefiting from a unique collaborative effort that's feeding a growing need for fresh and affordable goat meat. (April 18) Video provided by AP
Powered by NewsLook.com
Man Claims He Found Loch Ness Monster With... Apple Maps?

Man Claims He Found Loch Ness Monster With... Apple Maps?

Newsy (Apr. 18, 2014) Andy Dixon showed the Daily Mail a screenshot of what he believes to be the mythical beast swimming just below the lake's surface. 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:
from the past week

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