2. Academic Validation
  3. Inhibition of Staphylococcus aureus and biofilm formation by the anthelminthic drug, triclabendazole

Inhibition of Staphylococcus aureus and biofilm formation by the anthelminthic drug, triclabendazole

  • J Antibiot (Tokyo). 2022 May;75(5):287-295. doi: 10.1038/s41429-022-00515-9.
Jie Guo  # 1 2,  Yufang Zhang  # 1 3,  Hang Cheng  # 1,  Duoyun Li 1,  Zhanwen Wang 1,  Chengchun Chen 1,  Zhijian Yu 1 2,  Qiwen Deng 4 5,  Zewen Wen 6 7
Affiliations

Affiliations

  • 1 Department of Infectious Diseases and Shenzhen Key Laboratory for Endogenous Infections, Huazhong University of Science and Technology Union Shenzhen Hospital, No. 89 Taoyuan Road, Nanshan District, Shenzhen, 518052, China.
  • 2 Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University Health Science Center, Shenzhen, 518060, China.
  • 3 Class of Biological Science, Shenzhen College of International Education, No. 3 Antuoshan 6th Rd, Futian District, Shenzhen, 518040, China.
  • 4 Department of Infectious Diseases and Shenzhen Key Laboratory for Endogenous Infections, Huazhong University of Science and Technology Union Shenzhen Hospital, No. 89 Taoyuan Road, Nanshan District, Shenzhen, 518052, China. [email protected].
  • 5 Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University Health Science Center, Shenzhen, 518060, China. [email protected].
  • 6 Department of Infectious Diseases and Shenzhen Key Laboratory for Endogenous Infections, Huazhong University of Science and Technology Union Shenzhen Hospital, No. 89 Taoyuan Road, Nanshan District, Shenzhen, 518052, China. [email protected].
  • 7 Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University Health Science Center, Shenzhen, 518060, China. [email protected].
  • # Contributed equally.
PMID: 35288676 DOI: 10.1038/s41429-022-00515-9
Abstract

Triclabendazole (TBD) has been widely used in the treatment of helminthic Infection. The anti-biofilm activity and Antibacterial mechanism of TBD against Staphylococcus aureus were not known. Here, the anti-biofilm activity of TBD against clinical S. aureus isolates from China was systematically evaluated. Under TBD pressure, TBD-induced tolerant S. aureus with elevated TBD minimum inhibitory concentration (MIC) was selected in vitro and the genetic mutations between the parental isolates and TBD-induced tolerant derivatives were determined by whole-genome sequencing. TBD could significantly inhibit biofilm formation at sub-inhibitory concentration and disperse mature biofilm of clinical S. aureus isolates. In addition, TBD displayed bactericidal activity against the Bacterial cells embedded in the biofilm and showed anti-persisters activity. Proteomic analysis showed that KEGG pathways of ABC transporters and beta-lactam resistance were significantly changed after TBD exposure. Moreover, SAUSA300_RS08395 (molecular chaperone DnaK), SAUSA300_RS11200 (sensor histidine kinase KdpD), SAUSA300_RS06325 (DNA translocase FtsK) were identified as candidate targets of TBD in S. aureus. Overexpression experiments further demonstrated that the elevated transcriptional level of DnaK resulted in S. aureus growth delay after exposure to a sub-MIC concentration of 1/2× MIC TBD. In conclusion, TBD exhibits Antibacterial and anti-biofilm activity against S. aureus possibly by targeting the DnaK chaperone system.

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