Membrane-Interactive Compounds From Pistacia lentiscus L. Thwart Pseudomonas aeruginosa Virulence
Ali Tahrioui1, Sergio Ortiz2, Onyedikachi Cecil Azuama1
1Laboratoire de Microbiologie Signaux et Microenvironnement, LMSM EA4312, Université de Rouen Normandie, Normandie Université, Évreux, France.
Abstract:
Pseudomonas aeruginosa is capable to deploy a collection of virulence factors that are not only essential for host infection and persistence, but also to escape from the host immune system and to become more resistant to drug therapies. Thus, developing anti-virulence agents that may directly counteract with specific virulence factors or disturb higher regulatory pathways controlling the production of virulence armories are urgently needed. In this regard, this study reports that Pistacia lentiscus L. fruit cyclohexane extract (PLFE1) thwarts P. aeruginosa virulence by targeting mainly the pyocyanin pigment production by interfering with 4-hydroxy-2-alkylquinolines molecules production. Importantly, the anti-virulence activity of PLFE1 appears to be associated with membrane homeostasis alteration through the modulation of SigX, an extracytoplasmic function sigma factor involved in cell wall stress response. A thorough chemical analysis of PLFE1 allowed us to identify the ginkgolic acid (C17:1) and hydroginkgolic acid (C15:0) as the main bioactive membrane-interactive compounds responsible for the observed increased membrane stiffness and anti-virulence activity against P. aeruginosa. This study delivers a promising perspective for the potential future use of PLFE1 or ginkgolic acid molecules as an adjuvant therapy to fight against P. aeruginosa infections.
Insights
Pistacia lentiscus fruit extract combats Pseudomonas aeruginosa virulence by disrupting pyocyanin production and altering membrane function. Ginkgolic acids in the extract show promise as an adjuvant therapy against P. aeruginosa infections.
Area of Science:
- Microbiology
- Pharmacology
- Natural Product Chemistry
Background:
- Pseudomonas aeruginosa possesses virulence factors crucial for infection, immune evasion, and drug resistance.
- Developing anti-virulence agents is essential to combat P. aeruginosa infections.
- Targeting virulence factors or regulatory pathways offers a promising therapeutic strategy.
Purpose of the Study:
- To investigate the anti-virulence potential of Pistacia lentiscus L. fruit cyclohexane extract (PLFE1) against P. aeruginosa.
- To elucidate the mechanisms underlying PLFE1's anti-virulence activity.
- To identify the bioactive compounds responsible for the observed effects.
Main Methods:
- Treatment of P. aeruginosa with PLFE1.
- Analysis of pyocyanin pigment production and 4-hydroxy-2-alkylquinolines.
- Assessment of membrane homeostasis and SigX modulation.
- Chemical analysis of PLFE1 to identify active compounds.
Main Results:
- PLFE1 effectively reduced P. aeruginosa virulence, primarily by inhibiting pyocyanin production.
- PLFE1 interfered with 4-hydroxy-2-alkylquinolines synthesis.
- PLFE1 modulated membrane homeostasis via SigX, increasing membrane stiffness.
- Ginkgolic acid (C17:1) and hydroginkgolic acid (C15:0) were identified as key bioactive compounds.
Conclusions:
- PLFE1 exhibits significant anti-virulence activity against P. aeruginosa.
- Ginkgolic acids are the primary compounds responsible for PLFE1's effects.
- PLFE1 and its active components represent potential adjuvant therapies for P. aeruginosa infections.
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