Investigating Sulforaphane's anti-virulence and anti-quorum sensing properties against Pseudomonas aeruginosa

Mahmoud M Bendary; Mohamed A M Ali; Alyaa S Abdel Halim; Fehmi Boufahja; Anis Ahmad Chaudhary; Amr Elkelish; Rania H M Soliman; Wael A H Hegazy

doi:10.3389/fphar.2024.1406653

Investigating Sulforaphane's anti-virulence and anti-quorum sensing properties against Pseudomonas aeruginosa

Front Pharmacol. 2024 May 21:15:1406653. doi: 10.3389/fphar.2024.1406653. eCollection 2024.

Authors

Mahmoud M Bendary¹, Mohamed A M Ali^{2

3}, Alyaa S Abdel Halim³, Fehmi Boufahja², Anis Ahmad Chaudhary², Amr Elkelish^{2

4}, Rania H M Soliman⁵, Wael A H Hegazy^{6

7}

Affiliations

¹ Department of Microbiology and Immunology, Faculty of Pharmacy, Port Said University, Port Said, Egypt.
² Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia.
³ Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt.
⁴ Department of Botany and Microbiology, Faculty of Science, Suez Canal University, Ismailia, Egypt.
⁵ Department of Anatomy and Embryology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
⁶ Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
⁷ Pharmacy Program, Department of Pharmaceutical Sciences, Oman College of Health Sciences, Muscat, Oman.

Abstract

Background: P. aeruginosa, a significant bacterium, can cause severe illness and resistance to antibiotics. Quorum sensing (QS) systems regulate virulence factors production. Targeting QS could reduce bacteria pathogenicity and prevent antibiotic resistance. Cruciferous vegetables contain sulforaphane, known for its anti-inflammatory, antioxidant, anticancer, and antimicrobial properties.

Aim: We aimed to examine the inhibitory influences of sulforaphane, at a sub-inhibitory concentration (¼ minimum inhibitory concentration, MIC), on virulence and QS in P. aeruginosa.

Materials and methods: The sulforaphane's anti-virulence actions at sub-inhibitory concentrations were explored in vitro and in vivo. A sub-MIC concentration of sulforaphane was combined with anti-pseudomonal drugs, and the results of this combination were assessed. The virtual affinity of sulforaphane for the receptors of QS was studied, and its effect on the expression of QS genes was quantified.

Results: Sulforaphane significantly decreased the biofilm formation, motility, ability to withstand oxidative stress, and the synthesis of virulence extracellular enzymes such as proteases, hemolysins, and elastase, as well as other virulence factors like pyocyanin. In addition, sulforaphane lessened the severity of P. aeruginosa infection in mice. Sulforaphane reduced the antipseudomonal antibiotics' MICs when used together, resulting in synergistic effects. The observed anti-virulence impacts were attributed to the ability of sulforaphane to inhibit QS via suppressing the QS genes' expression.

Conclusion: Sulforaphane shows promise as a potent anti-virulence and anti-QS agent that can be used alongside conventional antimicrobials to manage severe infections effectively. Furthermore, this study paves the way for further investigation of sulforaphane and similar structures as pharmacophores for anti-QS candidates.

Keywords: Pseudomonas aeruginosa; Sulforaphane; bacterial virulence; quorum sensing; resistance to antibiotics.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported and funded by the Deanship of Scientific Research at Imam Mohammad Ibn Saud Islamic University (IMSIU) (grant number IMSIU-RP23083).