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

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