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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI141927-02
Application #
9964657
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Xu, Zuoyu
Project Start
2019-07-01
Project End
2021-06-30
Budget Start
2020-07-01
Budget End
2021-06-30
Support Year
2
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Oklahoma Norman
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
848348348
City
Norman
State
OK
Country
United States
Zip Code
73019