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Anti-quorum sensing potential of ketoprofen and its derivatives against Pseudomonas aeruginosa: insights to in silico and in vitro studies

Abstract

Antibiotics are usually used for the treatment of bacterial infections, but multidrug-resistant strains are a phenomenon that has been growing at an increasing rate worldwide. Thus, there is an increasing need for novel strategies for combatting infectious diseases. Many pathogenic bacteria apply quorum sensing (QS) to regulate their pathogenicity and virulence factors production. This circuit makes the QS system an attractive target for antibacterial therapy. In the present study, an important member of non-steroidal anti-inflammatory drugs (NSAIDs), by reducing the biofilm and producing QS-regulated virulence factors, ketoprofen and its synthetic derivatives were screened against the Pseudomonas aeruginosa PAO1. All compounds showed anti-biofilm activity (16–79%) and most of them presented anti-virulence activity. In the co-treatment of ketoprofen, G20, G21, or G77 with tobramycin, biofilm is significantly reduced (potentiated to > 50%) in the number of cells protected inside the impermeable matrix. The in silico studies in addition to the similarities between the chemical structures of PqsR natural ligands and ketoprofen derivatives reinforce the possibility that the mechanism of action is through PqsR inhibition. Based on the results, the anti-pathogenic effect was more appreciable in ketoprofen, G77, and G20.

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Data and materials are available as needed.

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Acknowledgement

The results described in this paper were part of pharmacy students thesis.

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VS and BSFB designed the study and revised the manuscript; EJ and MD performed the experiment and collected the data; RG coordinated the study; AST and SG analyzed the data and wrote the manuscript.

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Correspondence to Vahid Soheili or Bibi Sedigheh Fazly Bazzaz.

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Communicated by Erko Stackebrandt.

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Tajani, A.S., Jangi, E., Davodi, M. et al. Anti-quorum sensing potential of ketoprofen and its derivatives against Pseudomonas aeruginosa: insights to in silico and in vitro studies. Arch Microbiol (2021). https://doi.org/10.1007/s00203-021-02499-w

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Keywords

  • Pseudomonas aeruginosa
  • Microbial resistance
  • Anti-virulence compounds
  • Anti-biofilm
  • Ketoprofen