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Ostarine attenuates pyocyanin in Pseudomonas aeruginosa by interfering with quorum sensing systems

The Journal of Antibiotics volume 74, pages 863–873 (2021)Cite this article

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Abstract

Antimicrobial resistance has been an increasingly serious threat to global public health. Anti-virulence strategies are being developed to manage antibiotic resistance because they apply a lower selective pressure for antimicrobial-resistant pathogens than that created using traditional bactericides. We aimed to discover novel small molecules that can reduce the production of virulence factors in Pseudomonas aeruginosa and determine the mechanism of action underlying these effects. A clinical compound library was screened, and ostarine was identified as a potential anti-virulence agent. The effects of ostarine were studied via antimicrobial susceptibility testing, bacterial growth assays, pyocyanin quantitation assays, transcriptomic analysis, quorum sensing signal molecule quantification, and real-time PCR assays. Ostarine treatment significantly decreased the synthesis of pyocyanin without any bactericidal action. Besides, ostarine treatment did not affect the relative growth rate and cell morphology of bacteria. Treatment with ostarine interfered with quorum sensing by decreasing the transcription of genes associated with quorum sensing systems and the production of signalling molecules. The inhibition of ostarine on pyocyanin production and gene expression can be alleviated when signalling molecules were supplemented externally. Overall, ostarine may act as a novel anti-virulence agent that can attenuate P. aeruginosa pyocyanin by interfering with quorum sensing systems.

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Acknowledgements

This research was funded by the National Natural Science Foundation of China (grant numbers 81573475, 82104248), CAMS Initiative for Innovative Medicine (grant number 2016-I2M-3-014), National Mega-project for Innovative Drugs (grant number 2019ZX09721001), and Cultivation Fund Project of the National Natural Science Foundation in Beijing Children’s Hospital, Capital Medical University (grant number GPQN202001).

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Authors and Affiliations

  1. Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

    Limin Dong, Lang Sun, Xinxin Hu, Tongying Nie, Jing Pang, Xiukun Wang, Xinyi Yang, Congran Li, Youwen Zhang & Xuefu You

  2. Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China

    Limin Dong & Kaihu Yao

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  1. Limin Dong
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Correspondence to Youwen Zhang or Xuefu You.

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Dong, L., Sun, L., Hu, X. et al. Ostarine attenuates pyocyanin in Pseudomonas aeruginosa by interfering with quorum sensing systems. J Antibiot 74, 863–873 (2021). https://doi.org/10.1038/s41429-021-00469-4

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