New Collaborative Paper Published in Journal of Applied Microbiology (IF 4.0)

Very glad to share our recent article published in the Journal of Applied Microbiology (IF 4.0), a collaborative work developed in collaboration with the group of Prof. Manuel Simões (FEUP/LEPABE). This article entitled “Montelukast and cefoperazone act as antiquorum sensing and antibiofilm agents against Pseudomonas aeruginosa” explores the potential of drug repurposing to control biofilm-related infectious diseases, focusing on two well-established drugs: montelukast and cefoperazone.

Key Findings:
Cefoperazone’s Efficacy:
Quorum Sensing Inhibition: Cefoperazone effectively inhibited the Pqs quorum sensing (QS) system of Pseudomonas aeruginosa by hindering the production of key autoinducer molecules, 2-heptyl-4-hydroxyquinoline (HHQ) and 2-heptyl-3-hydroxy-4(1H)-quinolone (PQS). This was supported by in silico results.

Reduction in Virulence: The drug reduced pyocyanin production by 50%, a significant virulence factor of P. aeruginosa.
Synergistic Effects: When combined with ciprofloxacin, cefoperazone showed a synergistic effect, enhancing biofilm control.
Montelukast’s Limited Impact: Montelukast did not show significant effects on the inhibition of the Pqs system or on P. aeruginosa biofilm control.

This study provides strong evidence that cefoperazone can interact with the Pqs system, reducing the pathogenicity and virulence of P. aeruginosa. Cefoperazone’s potential to be used in combination with other antibiotics, such as ciprofloxacin, offers a promising strategy for enhancing biofilm control and combating bacterial infections.

Montelukast and cefoperazone act as antiquorum sensing and antibiofilm agents against Pseudomonas aeruginosa

Tatiana F Vieira, Miguel M Leitão, Nuno M F S A Cerqueira, Sérgio F Sousa, Anabela Borges, Manuel Simões

Journal of Applied Microbiology, Volume 135, Issue 5, May 2024, lxae088 | DOI: 10.1093/jambio/lxae088


Aims: Drug repurposing is an attractive strategy to control biofilm-related infectious diseases. In this study, two drugs (montelukast and cefoperazone) with well-established therapeutic applications were tested on Pseudomonas aeruginosa quorum sensing (QS) inhibition and biofilm control.
Methods and results: The activity of montelukast and cefoperazone was evaluated for Pqs signal inhibition, pyocyanin synthesis, and prevention and eradication of Ps. aeruginosa biofilms. Cefoperazone inhibited the Pqs system by hindering the production of the autoinducer molecules 2-heptyl-4-hydroxyquinoline (HHQ) and 2-heptyl-3-hydroxy-4(1H)-quinolone (the Pseudomonas quinolone signal or PQS), corroborating in silico results. Pseudomonas aeruginosa pyocyanin production was reduced by 50%. The combination of the antibiotics cefoperazone and ciprofloxacin was synergistic for Ps. aeruginosa biofilm control. On the other hand, montelukast had no relevant effects on the inhibition of the Pqs system and against Ps. aeruginosa biofilm.
Conclusion: This study provides for the first time strong evidence that cefoperazone interacts with the Pqs system, hindering the formation of the autoinducer molecules HHQ and PQS, reducing Ps. aeruginosa pathogenicity and virulence. Cefoperazone demonstrated a potential to be used in combination with less effective antibiotics (e.g. ciprofloxacin) to potentiate the biofilm control action.