Skip to main content

Confronting TB resistance

Jun. 11, 2018, 4:00 PM

by Niyati Vachharajani

Tuberculosis, caused by Mycobacterium tuberculosis, is a highly infectious lung disease in humans.Unfortunately, resistance to anti-tubercular medicines such as fourth-generation fluoroquinolones is on the rise. In most cases, fluoroquinolone resistance is caused by mutations in a bacterial enzyme called gyrase.

Compounds called M. tuberculosis gyrase inhibitors (MGIs) display activity against tuberculosis in cellular and animal models, but little is known of their interaction with the bacterial enzyme.

Neil Osheroff, PhD, and colleagues examined the mechanism of action of MGIs against purifiedM. tuberculosis gyrase. They report that MGIs effectively increase levels of gyrase-mediated single-stranded DNA breaks, which lead to chromosomal fragmentation, and maintain activity against commonly mutated fluoroquinolone-resistant forms of the enzyme.

This mechanistic study, reported in the journal ACS Infectious Diseases, provides an important insight into anti-tubercular drug activity. Furthermore, it highlights the use of MGIs as potent anti-tubercular medicines and their potential in overcoming the serious threat of multi-drug resistant tuberculosis.

This research was supported by the U.S. Department of Veterans Affairs (Merit Review Award) and the National Institutes of Health (grants GM126363, CA077373).

Send suggestions for articles to highlight in Aliquots and any other feedback about the column to aliquots@vanderbilt.edu

Recent Stories from VUMC News and Communications Publications

Our amazing skin

Vanderbilt Medicine

Our amazing skin

Biology and the beat

Vanderbilt Medicine

Biology and the beat

Community care

Vanderbilt Nurse

Community care

Survive and thrive

Hope

Survive and thrive

more