Resisting Resistance: Developing New Drugs to Combat Antibiotic Resistant Bacteria
Grover Waldrop, Department of Biological Sciences
As the problem of antibiotic resistant pathogenic bacteria steadily worsens there remains an urgent need to develop new antibiotics and new targets for antibiotics. Dr. Grover Waldrop, LSU Department of Biological Sciences, is working with a new target for antibiotics the enzyme acetyl-CoA carboxylase. This enzyme is involved in the synthesis of the bacterial cell membrane. If a molecule could be developed to inhibit the enzyme it would kill bacteria and serve as a lead for developing antibiotics. His team of researchers uses CAMD to determine the three-dimensional picture of the enzyme with the inhibitor bound. They use this picture of the inhibitor bound to the enzyme to guide modifications of the inhibitor until it is suitable for animal testing.
Overuse of antibiotics has created antibiotic resistant bacteria such as MRSA. In collaboration with Pfizer we are developing new antibiotics using structure-based drug design.
Antibiotic Development Using Structure-Based Drug Design
- We have a new antibacterial target: the enzyme acetyl-CoA carboxylase.
- At CAMD we determine the structure of potential antibiotic molecules bound to acetyl-CoA carboxylase using the PX beamline.
- The molecule is then modified by organic chemistry to make it more drug like and the structure of the new molecule bound to the enzyme is determined at CAMD.
- This process is repeated until a molecule acceptable for animal testing is generated.
