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

• Published in: Journal of antibiotics 2021-12, Vol.74 (12), p.863-873
• Main Authors: Dong, Limin, Sun, Lang, Hu, Xinxin, Nie, Tongying, Pang, Jing, Wang, Xiukun, Yang, Xinyi, Li, Congran, Yao, Kaihu, Zhang, Youwen, You, Xuefu
• Format: Article
• Language: English
• Subjects: 101/47; 38/77; 38/91; 631/154; 631/326; Anilides - pharmacology; Anti-Bacterial Agents - pharmacology; Antibiotic resistance; Antibiotics; Antimicrobial agents; Antimicrobial resistance; Assaying; Bacteriology; Biomedical and Life Sciences; Bioorganic Chemistry; Cell morphology; Cytology; Drug Resistance, Bacterial; Gene expression; Gene Expression Regulation, Bacterial - drug effects; Growth rate; Life Sciences; Medicinal Chemistry; Microbial Sensitivity Tests; Microbiology; Morphology; Organic Chemistry; Pseudomonas aeruginosa; Pseudomonas aeruginosa - drug effects; Pseudomonas aeruginosa - genetics; Pseudomonas aeruginosa - pathogenicity; Public health; Pyocyanin; Pyocyanine - genetics; Pyocyanine - metabolism; Quantitation; Quorum sensing; Quorum Sensing - drug effects; Signaling; Transcription; Transcriptomics; Virulence; Virulence - drug effects; Virulence Factors
• ISSN: 0021-8820; 1881-1469
• DOI: 10.1038/s41429-021-00469-4

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.