A thiazole orange derivative targeting the bacterial protein FtsZ shows potent antibacterial activity

Ning Sun, Yu Jing Lu, Fung Yi Chan, Ruo Lan Du, Yuan yuan Zheng, Kun Zhang, Lok Yan So, Ruben Abagyan, Chao Zhuo, Yun Chung Leung, Kwok Yin Wong

Research output: Journal article publicationJournal articleAcademic researchpeer-review

27 Citations (Scopus)

Abstract

The prevalence of multidrug resistance among clinically significant bacteria calls for the urgent development of new antibiotics with novel mechanisms of action. In this study, a new small molecule exhibiting excellent inhibition of bacterial cell division with potent antibacterial activity was discovered through cell-based screening. The compound exhibits a broad spectrum of bactericidal activity, including the methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus and NDM-1 Escherichia coli. The in vitro and in vivo results suggested that this compound disrupts the dynamic assembly of FtsZ protein and Z-ring formation through stimulating FtsZ polymerization. Moreover, this compound exhibits no activity on mammalian tubulin polymerization and shows low cytotoxicity on mammalian cells. Taken together, these findings could provide a new chemotype for development of antibacterials with FtsZ as the target.
Original languageEnglish
Article number855
JournalFrontiers in Microbiology
Volume8
Issue numberMAY
DOIs
Publication statusPublished - 11 May 2017

Keywords

  • Antibacterial activity
  • Bacterial resistance
  • Cell division
  • FtsZ inhibitor
  • FtsZ polymerization

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)

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