New Collaborative Paper Published in Microbial Pathogenesis (IF 3.8)

Very happy to share our recent collaborative paper entitled “Dual action of benzaldehydes: Inhibiting quorum sensing and enhancing antibiotic efficacy for controlling Pseudomonas aeruginosa biofilms” developed in collaboration with the group of Prof. Manuel Simões (FEUP/LEPABE) and Prof. Fernanda Borges (FCUP(CIQUP) and published in Microbial Pathogenesis (IR 3.8)

The study investigated the role of three structurally related benzaldehydes—4-hydroxybenzaldehyde, 4-hydroxy-3-methoxybenzaldehyde (vanillin), and 4-hydroxy-3,5-dimethoxybenzaldehyde (syringaldehyde)—in disrupting the quorum sensing (QS) systems of Pseudomonas aeruginosa. Quorum sensing is crucial for biofilm formation and antimicrobial resistance, making it a promising target for controlling bacterial pathogenicity and virulence.

Key Findings:

Inhibition of QS Systems:

  • The benzaldehydes were found to inhibit the las and pqs QS systems by more than 80%.
  • Molecular docking studies revealed that these benzaldehydes bind strongly to the receptor pockets of key QS proteins (LasR, PQSA, PQSE, PQSR).

Reduction in Virulence Factors:

  • Vanillin achieved a 48% reduction in pyocyanin production, a virulence factor of P. aeruginosa.

Enhanced Antibiotic Efficacy:

  • When combined with tobramycin, the benzaldehydes led to a 60% reduction in biofilm biomass and a 90% reduction in the metabolic activity of established biofilms.
  • Similar results were observed with ciprofloxacin, where 4-hydroxybenzaldehyde increased biofilm susceptibility, resulting in a 65% reduction in biomass.

Conclusion:

This study demonstrated that benzaldehydes are potent QS inhibitors and can enhance the antibiofilm activity of antibiotics like tobramycin and ciprofloxacin against P. aeruginosa. This dual action makes them promising candidates for developing new strategies to combat bacterial infections and antibiotic resistance.

Dual action of benzaldehydes: Inhibiting quorum sensing and enhancing antibiotic efficacy for controlling Pseudomonas aeruginosa biofilms

Authors: Miguel M. Leitão, Tatiana F. Vieira, Sérgio F. Sousa, Fernanda Borges, Manuel Simões, Anabela Borges

Journal: Microbial Pathogenesis (2024) | DOI: 10.1016/j.micpath.2024.106663

Abstract:

Quorum sensing (QS) has a central role in biofilm lifestyle and antimicrobial resistance, and disrupting these
signaling pathways is a promising strategy to control bacterial pathogenicity and virulence. In this study, the
efficacy of three structurally related benzaldehydes (4-hydroxybenzaldehyde, 4-hydroxy-3-methoxybenzaldehyde
(vanillin) and 4-hydroxy-3,5-dimethoxybenzaldehyde (syringaldehyde)) in disrupting the las and pqs systems
of Pseudomonas aeruginosa was investigated using bioreporter strains and computational simulations.
Additionally, these benzaldehydes were combined with tobramycin and ciprofloxacin antibiotics to evaluate
their ability to increase antibiotic efficacy in preventing and eradicating P. aeruginosa biofilms. To this end, the
total biomass, metabolic activity and culturability of the biofilm cells were determined. In vitro assays results
indicated that the aromatic aldehydes have potential to inhibit the las and pqs systems by > 80 %. Molecular
docking studies supported these findings, revealing the aldehydes binding in the same pocket as the natural
ligands or receptor proteins (LasR, PQSA, PQSE, PQSR). Benzaldehydes were shown to act as virulence factor
attenuators, with vanillin achieving a 48 % reduction in pyocyanin production. The benzaldehyde-tobramycin
combination led not only to a 60 % reduction in biomass production but also to a 90 % reduction in the
metabolic activity of established biofilms. A similar result was observed when benzaldehydes were combined
with ciprofloxacin. 4-Hydroxybenzaldehyde demonstrated relevant action in increasing biofilm susceptibility to
ciprofloxacin, resulting in a 65 % reduction in biomass. This study discloses, for the first time, that the benzaldehydes
studied are potent QS inhibitors and also enhancers of antibiotics antibiofilm activity against
P. aeruginosa.