Notre Dame bioorganic chemist Shahriar Mobashery, the Navari Family Chair in Life Sciences, is the 2008 recipient of an Astellas USA Foundation Award by the American Chemical Society for his work on antibiotic resistance and his important contributions to the understanding of the bacterial cell wall.
The Astellas Awards were established by the American Chemical Society to identify individuals or teams who exemplify the criterion of having significantly contributed to scientific research that improved public health through their contributions in the chemical and related sciences.
The Mobashery lab has been seeking new approaches to understand antibiotic-resistant superbacterium called MRSA, for methicillin-resistant Staphylococcus aureus. This variant of Staphyloccocus aureus surfaced in the early 1960s and has recently emerged as a serious health problem.
By figuring out how MRSA lives and thrives, the Mobashery group has enabled the development of strategies for killing this difficult organism. His research group recently discovered a new line of defense by focusing on a unique protein called penicillin-binding protein 2a (PBP 2a) that MRSA carry on the cell membrane. Previous work from the research group has shown that PBP 2a acts as a key defense mechanism by interacting with the bacterial cell wall to form a chemical barricade that is impervious to antibiotics.
Mobashery and his team investigated three new synthetic cephalosporin antibiotics, structural relatives of penicillins. The novel antibiotics appear to interact with PBP 2a in a unique way.
In addition, the Mobashery team made important progress in elucidating the three-dimensional structure of mesh-like network called peptidoglycan that comprises the major component of the cell wall.
Earlier efforts to pin down the three-dimensional structure of peptidoglycan repeatedly ended in either frustrating failure or limited success. In a paper published in the Proceedings of the National Academy of Sciences, Mobashery describes how he and his team were able to characterize for the first time the framework of peptidoglycan through a painstaking series of studies involving a 37-step synthetic procedure for the preparation of a fragment of the cell wall and its characterization by nuclear magnetic resonance and by computation to elucidate the structure.
The breakthrough gives scientists the means to understand with unprecedented clarity how the action of antibiotics like penicillin works to impair the structure of the cell wall. Similarly, glycopeptide antibiotics such as vancomycin interact with the cell wall itself and this structural information provides an opportunity to understand their functions as well.
The award carries a $30,000 prize. Mobashery and the other award recipients will be honored in August at the 236th American Chemical Society national meeting in Philadelphia.