Infection and Drug Resistance (Jan 2023)

In vitro and Intracellular Antibacterial Activity of Sudapyridine (WX-081) Against Tuberculosis

  • Xiao H,
  • Yu X,
  • Shang Y,
  • Ren R,
  • Xue Y,
  • Dong L,
  • Zhao L,
  • Jiang G,
  • Huang H

Journal volume & issue
Vol. Volume 16
pp. 217 – 224


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Hua Xiao,* Xia Yu,* Yuanyuan Shang, Ruyan Ren, Yi Xue, Lingling Dong, Liping Zhao, Guanglu Jiang, Hairong Huang National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug Resistant Tuberculosis Research; Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hairong Huang, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, No. 97 Ma Chang, Tongzhou District, Beijing, 101149, People’s Republic of China, Tel +86-10-89509159, Fax +86-10-89509160, Email [email protected]: Sudapyridine (WX-081) has exhibited equivalent efficacy than its counterpart parent drug bedaquiline (BDQ) but better safety profile against Mycobacterium tuberculosis (Mtb). Our study was aimed to evaluate in vitro activity of WX-081 against the clinical isolates of Mtb with different drug-resistance profiles and the intracellular bactericidal activity against the reference strain.Methods: The minimum inhibitory concentrations (MICs) of WX-081 and BDQ were tested against 114 Mtb clinical isolates. The intracellular activity of WX-081 and BDQ against the Mtb reference strain H37Rv in THP-1 cells was also evaluated in parallel.Results: The MICs for WX-081 of the enrolled isolates ranged from 0.0156 μg/mL to 1 μg/mL. The MIC50 and MIC90 of WX-081 were, respectively, 0.25 μg/mL and 0.5 μg/mL, with 95.6% of the enrolled strains having MICs ≤ 0.25 μg/mL. For a given strain, the MIC value of WX-081 was generally equivalent to or 2-fold than MIC of BDQ. The intracellular bacterial killing was acquired with the tested drug concentrations that were presumed attainable during clinical usage.Conclusion: WX-081 exhibited potent efficacy against the clinical isolates in vitro. The intracellular killing effect of sudapyridine against the reference strain supports its potential efficacy in treating TB patients.Keywords: tuberculosis, sudapyridine, bedaquiline, antibacterial activity