Beyond the stomach: Repurposing bismuth tripotassium dicitrate as a novel strategy against multidrug-resistant Mycobacterium abscessus.

BACKGROUND/PURPOSE: Mycobacterium abscessus is a rapidly growing nontuberculous mycobacterium characterized by extensive antibiotic resistance, presenting substantial challenges in clinical management. This study aimed to identify potential antimicrobial agents repurposed from an FDA-approved drug library to combat M. abscessus infection.

METHODS

An initial high-throughput screen of 2680 FDA-approved drugs was conducted to identify compounds with antimicrobial activity against M. abscessus. Promising hits were further assessed through resazurin-based minimum inhibitory concentration (MIC) assays and MTT cytotoxicity assays using multidrug-resistant (MDR)-M. abscessus clinical isolates and various human cells, respectively. Moreover, the interactions of hit compounds with conventional antibiotics were assessed using the checkerboard assay.

RESULTS

The primary screen identified 39 nonantibiotic compounds with antibacterial activity against M. abscessus. Of these, eight exhibited favourable therapeutic indices on the basis of the MIC and cytotoxicity profiles. Among them, bismuth tripotassium dicitrate (BTD) emerged as the most promising candidate, demonstrating potent activity against multidrug-resistant clinical isolates, minimal cytotoxicity to multiple human cell lines, and significant synergy with clarithromycin and erythromycin.

CONCLUSION

BTD has strong efficacy against M. abscessus and favourable safety and synergy profiles. These findings support its potential for repurposing as a novel therapeutic for M. abscessus infections.