Featured Research

from universities, journals, and other organizations

Researchers uncover keys to antibiotic resistance in MRSA

Date:
October 4, 2013
Source:
University of Notre Dame
Summary:
Researchers have published research results this week that show how methicillin-resistant Staphylococcus aureus (MRSA) regulates the critical crosslinking of its cell wall in the face of beta-lactam antibiotics.

Methicillin-resistant Staphylococcus aureus (MRSA) is shown in the background (in gray). This figure depicts domains and key ligands of the penicillin binding protein 2a — a key resistance enzyme. The red molecule on the right is ceftaroline, a drug recently approved by the FDA.
Credit: University of Notre Dame

University of Notre Dame researchers Shahriar Mobashery and Mayland Chang and their collaborators in Spain have published research results this week that show how methicillin-resistant Staphylococcus aureus (MRSA) regulates the critical crosslinking of its cell wall in the face of beta-lactam antibiotics.

The work, published in the Proceedings of the National Academy of Sciences, reveals the mechanistic basis for how the MRSA bacterium became such a difficult pathogen over the previous 50 years, in which time it spread rapidly across the world. Modern strains of MRSA have become broadly resistant to antibiotics, including beta-lactam antibiotics, such as penicillins. In their report, the researchers disclose the discovery of an allosteric domain in the X-ray structure of the penicillin binding protein 2a of MRSA, the enzyme that carries out the crosslinking reaction. (An allosteric site is a place on the protein where its activity is regulated by the binding of another molecule.)

Mobashery, Chang and Juan Hermoso at CSIC, the Spanish Research Council, document that an allosteric trigger by a fragment of the cell wall at a distance of 60 Εngstroms (6 nanometers) activates a set of conformational changes that culminates in the opening of the active site from a closed conformation, enabling catalysis for the physiological role of the enzyme.

They also document that the new beta-lactam antibiotic ceftaroline, recently approved by the Food and Drug Administration, is able to bind to the allosteric domain and trigger the same allosteric opening of the active site. This subversion of the allosteric control allows another molecule of ceftaroline to access the active site, which inhibits the function of the enzyme, leading to cell death by MRSA. This mechanism of action for the antibiotic is unprecedented and offers important insights for design of future drugs to combat MRSA.

MRSA has been a difficult hospital pathogen to control and has emerged in the broader community in the past several years, especially in such places as prisons, locker rooms and nurseries. In the United States alone, the disease infects about 100,000 people and claims the lives of nearly 20,000 people annually.


Story Source:

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


Journal Reference:

  1. L. H. Otero, A. Rojas-Altuve, L. I. Llarrull, C. Carrasco-Lopez, M. Kumarasiri, E. Lastochkin, J. Fishovitz, M. Dawley, D. Hesek, M. Lee, J. W. Johnson, J. F. Fisher, M. Chang, S. Mobashery, J. A. Hermoso. How allosteric control of Staphylococcus aureus penicillin binding protein 2a enables methicillin resistance and physiological function. Proceedings of the National Academy of Sciences, 2013; DOI: 10.1073/pnas.1300118110

Cite This Page:

University of Notre Dame. "Researchers uncover keys to antibiotic resistance in MRSA." ScienceDaily. ScienceDaily, 4 October 2013. <www.sciencedaily.com/releases/2013/10/131004154805.htm>.
University of Notre Dame. (2013, October 4). Researchers uncover keys to antibiotic resistance in MRSA. ScienceDaily. Retrieved September 16, 2014 from www.sciencedaily.com/releases/2013/10/131004154805.htm
University of Notre Dame. "Researchers uncover keys to antibiotic resistance in MRSA." ScienceDaily. www.sciencedaily.com/releases/2013/10/131004154805.htm (accessed September 16, 2014).

Share This



More Plants & Animals News

Tuesday, September 16, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Some Tobacco Farmers Thrive Amid Challenges

Some Tobacco Farmers Thrive Amid Challenges

AP (Sep. 16, 2014) — The South's tobacco country is surviving, and even thriving in some cases, as demand overseas keeps growers in the fields of one of America's oldest cash crops. (Sept. 16) Video provided by AP
Powered by NewsLook.com
Scientists Given Rare Glimpse of 350-Kilo Colossal Squid

Scientists Given Rare Glimpse of 350-Kilo Colossal Squid

AFP (Sep. 16, 2014) — Scientists say a female colossal squid weighing an estimated 350 kilograms (770 lbs) and thought to be only the second intact specimen ever found was carrying eggs when discovered in the Antarctic. Duration: 00:47 Video provided by AFP
Powered by NewsLook.com
Raw: Scientists Examine Colossal Squid

Raw: Scientists Examine Colossal Squid

AP (Sep. 16, 2014) — Squid experts in New Zealand thawed and examined an unusual catch on Tuesday: a colossal squid. It was captured in Antarctica's remote Ross Sea in December last year and has been frozen for eight months. (Sept. 16) Video provided by AP
Powered by NewsLook.com
Ivorians Abandon Monkey Pets in Fear Over Ebola Virus

Ivorians Abandon Monkey Pets in Fear Over Ebola Virus

AFP (Sep. 16, 2014) — Since the arrival of Ebola in Ivory Coast, Ivorians have been abandoning their pets, particularly monkeys, in the fear that they may transmit the virus. Duration: 00:47 Video provided by AFP
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