Sanjib Bhakta
University of London, Uk
Title: Common non-steroidal anti-inflammatory drugs (NSAIDs) in the fight against tuberculosis (TB)
Biography
Biography: Sanjib Bhakta
Abstract
Tuberculosis (TB) remains a serious healthcare issue, more than two decades on from the first time it was declared as a global health emergency. Control of the disease has become increasingly difficult because of the alarming rise of antibiotic resistance in Mycobacterium tuberculosis, the etiological agent of TB. Development of new and effective drugs with novel mechanisms of action is thus of paramount importance to tackle antibiotic resistance. Novel chemical entities require at least a decade to be commercially available and repurposing drugs offers a solution to circumvent the investment of time and other resources (1). Certain common non-steroidal anti-inflammatory drugs (NSAIDs) have proven to be selectively bactericidal against replicating, non-replicating and multi-drug-resistant clinical isolates of M. tuberculosis (2, 3). Our primary focus is to repurpose carprofen and investigate their novel mechanisms of action in M. tuberculosis to help design more potent inhibitors in the future. To this effect we have followed both target-based and whole-cell approaches. Whole-cell transcriptomic analyses have revealed the effects of the drugs on a selected set of genes involved in key metabolic pathways that also play essential roles in antimicrobial resistance. Furthermore, the NSAIDs showed influence on the expression levels of proteins involved in cell-wall homeostasis and dormancy mechanisms. The most active NSAID, Carprofen was found to be a bactericidal drug that also inhibited the formation of mycobacterial biofilms and exhibited strong efflux pump inhibitory properties thus demonstrating their great potential in reversing antibiotic resistance.