Membrane-Interactive Compounds From Pistacia lentiscus L. Thwart Pseudomonas aeruginosa Virulence

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.

Traditional Chinese Medicine Tanreqing Inhibits Quorum Sensing Systems in Pseudomonas aeruginosa

“…The reduced pqsE gene expression would therefore disrupt the RhlR-mediated virulence gene expression. Additionally, the down-regulation of pqsBCDE will lead to quenching of the pqs system in P. aeruginosa and further contribute to reduced virulence (Deziel et al, 2005;Tahrioui et al, 2020). Collectively, all these evidences indicated that TRQ treatment could effectively target the pqs system and subsequently contribute to the inhibition of QS systems in P. aeruginosa.…”

“…For example, furanone C-30 (Hentzer et al, 2002), gingerol (Kim et al, 2015) and garlic extract (Rasmussen et al, 2005) have been reported to possess anti-QS activities. Recently, it has been demonstrated that ginkgolic acids from Pistacia lentiscus fruits inhibit P. aeruginosa virulence by targeting the pqs system (Tahrioui et al, 2020). Particularly, many traditional Chinese medicines have been shown to exert anti-QS and anti-virulence activities.…”

Identification of alkylsalicylic acids in Lentisk oil (Pistacia lentiscusL.) and cytotoxicity on Human Normal Dermal Fibroblasts

“…As this is the first report demonstrating the occurence of alkylphenols or alkylsalicylic acids in Pistacia lentiscus L. oil, HPLC-DAD-MS analysis was envisaged with comparison of oil samples 1-14 to the 3-(heptadec-8-en-1-yl)-salicylic acid standard from PLFE1 fruit fraction. PLFE1 is a non-polar fraction rich in alkylsalicylic acids, is isolated from fruits of Algerian Pistacia lentiscus and characterized in a previous work (Tahrioui et al, 2020). PLFE1 contains 3-(heptadec-8-en-1-yl)-salicylic acid, also known as ginkgolic acid (C17:1), together with hydroginkgolic acid (C15:0).…”

MeJA Elicitation of Chicory Hairy Roots Promotes Efficient Increase of 3,5-diCQA Accumulation, a Potent Antioxidant and Antibacterial Molecule

“…Pyocyanin, a phenazine-derived blue-green pigment is a redox-active secondary metabolite promoting the colonization and the dissemination of the bacterium. The green fluorescent pigment pyoverdine is a Fe 3+ high affinity siderophore [ 53 ]. Iron homeostasis plays a central role in bacterial growth and survival, and P. aeruginosa has developed several strategies to chelate iron from the available environmental iron sources, among which the catechol-derived siderophore pyoverdine.…”

“…After incubation for 24 h, cell growth was determined by measuring the OD at 580 nm. A pyocyanin quantification assay was carried out as described previously [ 53 ]. Briefly, one volume of chloroform was used to extract free-cell supernatants samples.…”