Navigation Links
Notre Dame researchers demonstrate antibiotic sensing event central to MSRA antibiotic resistance
Date:9/15/2011

A new paper by a team of University of Notre Dame researchers that included Shahriar Mobashery, Jeffrey Peng, Brian Baker and their researchers Oleg Borbulevych, Malika Kumararasiri, Brian Wilson, Leticia Llarrull, Mijoon Lee, Dusan Hesek and Qicun Shi describes a unique process that is central to induction of antibiotic resistance in the problematic bacterium methicillin-resistant Staphylococcus aureus (MSRA).

MRSA first emerged in the United Kingdom in 1961and spread rapidly across the globe. Modern strains of MRSA are broadly resistant to antibiotics of various classes, but resistance to B-lactam antibiotics, which include penicillins, cephalosporins, and carpapenems, is an acute problem because it impacts virtually all commercially available members of the class.

Earlier research by Mobashery, who holds the Navari Family Chair of Life Sciences at Notre Dame, found that an antibiotic sensor/signal transducer protein called "BlaR1" is a key player in MRSA's resistance to β-lactam antibiotics. Specifically, he had detected by spectroscopy a unique recognition process by the BlaR1 protein of the antibiotic that the organism might encounter. This recognition event, termed "Lysine N-Decarboxylation Switch," involved formation of an N-carboxylated lysine within the antibiotic-binding domain of BlaR1, which experiences decarboxylation on binding to the antibiotic. This decarboxylation gives the antibiotic complex longevity, which benefits MRSA in the face of the antibiotic challenge. Although this antibiotic-recognition event was described by Mobashery's research group a few years earlier, the process was not visualized in atomic resolution, despite attempts by several other research groups.

The three collaborating groups of Notre Dame researchers approached the problem differently. The Peng group studies the process by three- and two-dimensional NMR spectroscopy in Notre Dame's Lizzardo Magnetic Resonance Research Center, the Baker group grew new crystals of the protein for x-ray diffraction and the Mobashery group applied computational methods to understand the process.

The efforts paid off, as Peng demonstrated the presence of N-carboxylated lysine in the protein and showed that it undergoes N-decarboxylation on binding to the antibiotic in solution. Baker visualized both the N-carboxylated lysine in the x-ray crystal structure of the uncomplexed form and showed that when the antibiotic complexed with the protein, the N-decarboxylation switch resulted in a stable complex critical to the manifestation of resistance.

The lysine N-decarboxylation switch triggers MRSA's antibiotic sensor domain to adopt the active state that leads to all the subsequent biochemical processes that enable resistance, an event that was investigated by computational analyses in the Mobashery lab in the present study.

The importance of this lysine N-decarboxylation switch for MRSA rests in the fact that the organism does not mobilize its resources until and unless it is exposed to the antibiotic. As such, in an economy of existence, the MRSA conserves its resources until BlaR1 informs it that it has come in contact with a B-lactam antibiotic.

The research paper describing the team's findings appears in the Journal of Biological Chemistry.


'/>"/>

Contact: Shahriar Mobashery
mobashsery@nd.edu
574-631-2932
University of Notre Dame
Source:Eurekalert

Related biology news :

1. Notre Dame research reveals brain network connections
2. Breakthrough in Niemann-Pick Type C research reported by Notre Dame and Cornell scientists
3. Notre Dame research offers important clues about grasshopper population explosions
4. Notre Dame biologists call for regulation of rare plant sales
5. Notre Dame researcher helps discover walking properties of bacteria
6. Notre Dame and Wyoming scientists genetically engineer silkworms to produce artificial spider silk
7. Twins are intriguing research subjects for Notre Dame biometircs researchers
8. Notre Dame study focuses on protein dynamics
9. Notre Dame researchers describe new tool for evaluating managed relocations
10. Researchers uncover a potential new benefit of pure maple syrup on liver health
11. EPA grants help Wayne State researchers stave off Great Lakes environmental invaders
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/18/2016)... JOSE, Calif. , Jan. 18, 2016 /PRNewswire/ ... security software that simplifies the use and access ... technology and go-to-market partnership with American Cyber.  ... Cyber brings extensive experience leading transformational C4ISR and ... implementing and integrating the latest proven technology solutions," ...
(Date:1/13/2016)... ALBANY, New York , January 13, 2016 /PRNewswire/ ... Transparency Market Research has published a new market report ... Share, Growth, Trends, and Forecast, 2015 - 2023. According to ... mn in 2014 and is anticipated to reach US$1,625.8 ... from 2015 to 2023. In terms of volume, the ...
(Date:1/11/2016)... , Jan. 11, 2016 Synaptics Incorporated ... interface solutions, today announced that its ClearPad ® ... (TDDI) products won two separate categories in the 8 ... Innovator and Best Technology Breakthrough. The Synaptics ® ... a simplified supply chain, thinner devices, brighter displays and ...
Breaking Biology News(10 mins):
(Date:2/12/2016)... , Feb. 12, 2016  PTC Therapeutics, Inc. ... annual STRIVE (Strategies to Realize Innovation, Vision and ... (DMD). STRIVE provides funds to patient advocacy organizations ... make meaningful contributions to the rare disease community ... of future patient advocates. Mary ...
(Date:2/11/2016)... NBIX ) today announced its financial results for the quarter ... --> For the fourth quarter of 2015, the ... per share, compared to a net loss of $19.4 million, or ... the year ended December 31, 2015, the Company reported a net ... to a net loss of $60.5 million, or $0.81 loss per ...
(Date:2/11/2016)... , Feb. 11, 2016  Bioethics International, a not-for-profit organization ... researched, developed, marketed and made accessible to patients around the ... had named the publication of the Good Pharma ... publication is also featured as one of BMJ Open ... last year that are most frequently read. Ed ...
(Date:2/11/2016)... (PRWEB) , ... February 11, ... ... business-to-business publication dedicated to delivering cutting-edge information focused on the development and ... Sciences to become a premier sponsor of the 2016 BioProcess International Awards ...
Breaking Biology Technology: