Antimicrobial Activity of Trigonelline Hydrochloride Against Pseudomonas aeruginosa and Its Quorum-Sensing Regulated Molecular Mechanisms on Biofilm Formation and Virulence

Abstract

Pseudomonas aeruginosa, a vivid biofilm-producing bacterium, is considered a dreadful opportunistic pathogen, and thus, management of biofilm-associated infections due to multidrug resistant strains by traditional drugs currently is of great concern. This study was aimed to assess the impact of trigonelline hydrochloride, a pyridine alkaloid, on P. aeruginosa PAO1, in search of an alternative therapeutant. The effect of trigonelline on colony morphology and motility was studied along with its role on biofilm and expression virulence factors. Trigonelline influenced the colony structure, motility, biofilm architecture, and the production of virulence factors in a dose-dependent manner. Alterations in quorum sending (QS)-regulated gene expression after treatment and molecular docking analysis for certain regulator proteins confirmed its effect on the QS-system network by affecting Las, Rhl, and Pqs signaling pathways and as possible molecular targets. Thus, trigonelline might be considered as a potential chemical lead to manage biofilm-associated pathogenesis or to develop other analogues with enhanced pharmacokinetic actions.

Ferroptosis in Cancer Therapy: Mechanisms, Small Molecule Inducers, and Novel Approaches

“…100 Trigonelline, the primary alkaloidal component of the legume herbaceous Trigonella foenum-graecum, exhibits anti-HSV-1, antibacterial, and antifungal activities. 185 Acting as an Nrf2 inhibitor, trigonelline reduces cellular resistance to ferroptosis and shows potential for combination therapy with other ferroptosis inducers. 101 In xenograft models, trigonelline enhances the anticancer effects of erastin, sorafenib, and RSL3, and increases the chemosensitivity of Etoposide in pancreatic cancer.…”