Novel Antibacterial Activity of Febuxostat, an FDA-Approved Antigout Drug against Mycobacterium tuberculosis Infection

Lee Han Kim, Soon Myung Kang, Jake Whang, Kee Woong Kwon, Sung Jae Shin

Research output: Contribution to journalArticlepeer-review


Accumulating evidence suggests that drug repurposing has drawn attention as an anticipative strategy for controlling tuberculosis (TB), considering the dwindling drug discovery and development pipeline. In this study, we explored the antigout drug febuxostat and evaluated its antibacterial activity against Mycobacterium species. Based on MIC evaluation, we found that febuxostat treatment significantly inhibited mycobacterial growth, especially that of Mycobacterium tuberculosis (Mtb) and its phylogenetically close neighbors, M. bovis, M. kansasii, and M. shinjukuense, but these microorganisms were not affected by allopurinol and topiroxostat, which belong to a similar category of antigout drugs. Febuxostat concentration-dependently affected Mtb and durably mediated inhibitory functions (duration, 10 weeks maximum), as evidenced by resazurin micro-titer assay, time-kill curve analysis, phenotypic susceptibility test, and the Bactec MGIT 960 system. Based on these results, we determined whether the drug shows antimycobacterial activity against Mtb inside murine bone marrow-derived macrophages (BMDMs). Notably, febuxostat markedly suppressed the intracellular growth of Mtb in a dose-dependent manner without affecting the viability of BMDMs. Moreover, orally administered febuxostat was efficacious in a murine model of TB with reduced bacterial loads in both the lung and spleen without the exacerbation of lung inflammation, which highlights the drug potency. Taken together, unexpectedly, our data demonstrated that febuxostat has the potential for treating TB.

Original languageEnglish
JournalAntimicrobial agents and chemotherapy
Issue number9
Publication statusPublished - 2022 Sept

Bibliographical note

Funding Information:
This work was supported by National Research Foundation of Korea (NRF) grants funded by the Korea government (MSIT) (NRF-2019R1A2C2003204 and NRF-2020R1C1C1010171) and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare (HI22C0177), Republic of Korea. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright:
© 2022 American Society for Microbiology. All Rights Reserved.

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases


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