Doctor of Philosophy (PhD)
The rise of antibacterial resistant bacteria is a major problem in the United States of America and around the world. Millions of patients are infected with antimicrobial resistant bacteria each year. Novel antibacterial agents are needed to combat the growing and present crisis. Acetyl-CoA carboxylase (ACC), the multi-subunit complex which catalyses the first committed step in fatty acid synthesis, is a validated target for antibacterial agents. However, there are at present, no commercially available antibiotics that target ACC. Ethyl 4-[[2-chloro-5-(phenylcarbamoyl)phenyl]sulfonylamino]benzoate (SABA1) is a compound that has been shown to have antibacterial properties against Pseudomonas aeruginosa and Escherichia coli. SABA1 inhibits biotin carboxylase (BC), the enzyme that catalyses the first half reaction of ACC. SABA1 inhibits BC via an atypical mechanism. It binds in the biotin binding site in the presence of ADP. Pyrrolocin C (PYRC) and Equisetin (EQI) are two natural products that have been shown to have antibacterial properties against Gram positive organisms and both compounds inhibit BC. However, unlike all other known inhibitors of BC with antibacterial properties which bind in the active site, PYRC and EQI bind allosterically. SABA1, PYRC, and EQI represents two potentially new classes of antibiotics that can be used to combat the antibacterial resistance crisis.
Craft, Matt, "Inhibition of Biotin Carboxylase by Three Antibacterial Compounds" (2022). LSU Doctoral Dissertations. 5751.
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