Small molecule inhibitors of bacterial condensins ABSTRACT The emergence and spread of antibiotic resistant pathogenic bacteria presents a rapidly expanding threat to public health. Among enteric bacteria, in particular, several species have evolved that are resistant to all presently available antibiotics resulting in high mortality rates among affected patients. This proposal aims to develop bacterial condensins as a novel antimicrobial drug target. Condensins play a central role in chromosome organization, an essential cellular function, and are required for cell viability and pathogenicity in a diverse range of organisms. Bacterial and eukaryotic condensins display sufficient sequence divergence to expect the existence of highly selective inhibitors. The applicant has recently developed and validated a novel high throughput screening cascade for condensin inhibitors. This proposal seeks to perform the screen on a large library of compounds and natural products. The results will likely yield novel chemical probes for chromosome biology and new chemical scaffolds against a novel target suitable for further preclinical development.
The spread of multidrug resistant bacteria often leads to mortality rates above 50%. This project seeks to discover small molecule inhibitors that would be effective against such pathogens. Further development of this research will likely yield new antimicrobial agents effective against drug resistant pathogens.
