AUTHOR=Sun Ning , Lu Yu-Jing , Chan Fung-Yi , Du Ruo-Lan , Zheng Yuan-yuan , Zhang Kun , So Lok-Yan , Abagyan Ruben , Zhuo Chao , Leung Yun-Chung , Wong Kwok-Yin TITLE=A Thiazole Orange Derivative Targeting the Bacterial Protein FtsZ Shows Potent Antibacterial Activity JOURNAL=Frontiers in Microbiology VOLUME=8 YEAR=2017 URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2017.00855 DOI=10.3389/fmicb.2017.00855 ISSN=1664-302X 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.