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Madurahydroxylactone, an Inhibitor of Staphylococcus aureus FtsZ from Nonomuraea sp. AN100570

  • Kim, Bo-Min (Superbacteria Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Choi, Ha-Young (Superbacteria Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim, Geon-Woo (Superbacteria Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Zheng, Chang-Ji (Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Yanbian University College of Pharmacy) ;
  • Kim, Young-Ho (Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Yanbian University College of Pharmacy) ;
  • Kim, Won-Gon (Superbacteria Research Center, Korea Research Institute of Bioscience and Biotechnology)
  • Received : 2017.08.18
  • Accepted : 2017.09.06
  • Published : 2017.11.28

Abstract

FtsZ, a bacterial cell-division protein, is an attractive antibacterial target. In the screening for an inhibitor of Staphylococcus aureus FtsZ, madurahydroxylactone (1) and its related derivatives 2-5 were isolated from Nonomuraea sp. AN100570. Compound 1 inhibited S. aureus FtsZ with an $IC_{50}$ of $53.4{\mu}M$ and showed potent antibacterial activity against S. aureus and MRSA with an MIC of $1{\mu}g/ml$, whereas 2-5 were weak or inactive. Importantly, 1 induced cell elongation in the cell division phenotype assay, whereas 2-5 did not. It indicates that 1 exhibits its potent antibacterial activity via inhibition of FtsZ, and the hydroxyl group and hydroxylactone ring of 1 are critical for the activity. Thus, madurahydroxylactone is a new type of inhibitor of FtsZ.

Keywords

References

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