PMID- 36040172
OWN - NLM
STAT- MEDLINE
DCOM- 20220923
LR  - 20230301
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Print)
IS  - 0066-4804 (Linking)
VI  - 66
IP  - 9
DP  - 2022 Sep 20
TI  - Novel Antibacterial Activity of Febuxostat, an FDA-Approved Antigout Drug against 
      Mycobacterium tuberculosis Infection.
PG  - e0076222
LID - 10.1128/aac.00762-22 [doi]
LID - e00762-22
AB  - 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 microtiter 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.
FAU - Kim, Lee-Han
AU  - Kim LH
AUID- ORCID: 0000-0003-3402-1769
AD  - Department of Microbiology, Yonsei University College of Medicine, Seoul, South 
      Korea.
AD  - Institute for Immunology and Immunological Disease, Yonsei University College of 
      Medicine, Seoul, South Korea.
FAU - Kang, Soon Myung
AU  - Kang SM
AD  - Department of Microbiology, Yonsei University College of Medicine, Seoul, South 
      Korea.
AD  - Brain Korea 21 Project for Graduate School of Medical Science, Yonsei University 
      College of Medicine, Seoul, South Korea.
FAU - Whang, Jake
AU  - Whang J
AUID- ORCID: 0000-0003-4444-508X
AD  - Korea Mycobacterium Resource Center (KMRC) & Basic Research Section, The Korean 
      Institute of Tuberculosis (KIT), Cheongju-si, Chungcheongbuk-do, South Korea.
FAU - Kwon, Kee Woong
AU  - Kwon KW
AUID- ORCID: 0000-0002-6259-855X
AD  - Department of Microbiology, Yonsei University College of Medicine, Seoul, South 
      Korea.
AD  - Brain Korea 21 Project for Graduate School of Medical Science, Yonsei University 
      College of Medicine, Seoul, South Korea.
FAU - Shin, Sung Jae
AU  - Shin SJ
AUID- ORCID: 0000-0003-0854-4582
AD  - Department of Microbiology, Yonsei University College of Medicine, Seoul, South 
      Korea.
AD  - Institute for Immunology and Immunological Disease, Yonsei University College of 
      Medicine, Seoul, South Korea.
AD  - Brain Korea 21 Project for Graduate School of Medical Science, Yonsei University 
      College of Medicine, Seoul, South Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220830
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Antitubercular Agents)
RN  - 101V0R1N2E (Febuxostat)
RN  - 63CZ7GJN5I (Allopurinol)
SB  - IM
MH  - Allopurinol
MH  - Animals
MH  - Antitubercular Agents/pharmacology/therapeutic use
MH  - Febuxostat/pharmacology/therapeutic use
MH  - Mice
MH  - *Mycobacterium tuberculosis
MH  - *Tuberculosis/drug therapy/microbiology
PMC - PMC9487535
OTO - NOTNLM
OT  - Mycobacterium tuberculosis
OT  - febuxostat
OT  - in vivo efficacy testing
OT  - intracellular drug susceptibility test
OT  - minimum inhibitory concentrations
COIS- The authors declare no conflict of interest.
EDAT- 2022/08/31 06:00
MHDA- 2022/09/24 06:00
PMCR- 2023/02/28
CRDT- 2022/08/30 09:04
PHST- 2022/08/31 06:00 [pubmed]
PHST- 2022/09/24 06:00 [medline]
PHST- 2022/08/30 09:04 [entrez]
PHST- 2023/02/28 00:00 [pmc-release]
AID - 00762-22 [pii]
AID - aac.00762-22 [pii]
AID - 10.1128/aac.00762-22 [doi]
PST - ppublish
SO  - Antimicrob Agents Chemother. 2022 Sep 20;66(9):e0076222. doi: 
      10.1128/aac.00762-22. Epub 2022 Aug 30.