Poster Presentation BACPATH 2017

Cell division as a target for the development of novel antimicrobial agents (#112)

Wern Chai 1 , Susan Semple 1 , Heather Rickard 1 , Rietie Venter 1
  1. School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia

Antibiotic resistance has been an on-going concern to the health care community. It presents a global threat that necessitates urgent development of agents with novel mechanisms of action. In prokaryotic cells, the filamentous temperature sensitive Z-ring (FtsZ) represents an attractive target for development of novel anti-microbial agents. FtsZ is an essential protein which is homologous to tubulin from eukaryotes which plays a crucial role in cell division. In this study, a collection of compounds synthesized by our collaborators from Shandong University was tested for their ability to inhibit FtsZ. At first, it was determined if the compounds had any anti-bacterial activity by measure the minimum inhibitory concentration and minimum bactericidal concentration for each compound against a series of Gram-positive and Gram-negative bacteria. The ability of the compounds to inhibit cellular division was investigated by measuring cell elongation (bacilli) or cell ballooning (cocci). Additionally, the effect of the compounds on mammalian tubulin was also determined to ensure they only target the bacterial FtsZ protein. The compounds showed anti-bacterial activity with MIC values between 4 to 256 µg/mL. Selected compounds were able to inhibit cell division in MRSA and Acinetobacter baummanii. None of the compounds tested had any effect on mammalian tubulin polymerisation. With this study, we have identified promising new anti-microbial compounds that selectively inhibit bacterial cell division and could be further developed into novel antimicrobials targeting the bacterial FtsZ protein.