Abstract
Several plant extracts exhibit anti-virulence properties due to the interruption of bacterial quorum sensing (QS). However, studies on their effects at the preclinical level are scarce. Here, we used a murine model of abscess/necrosis induced by Pseudomonas aeruginosa to evaluate the anti-pathogenic efficacy of 24 plant extracts at a sub-inhibitory concentration. We analyzed their ability to inhibit QS-regulated virulence factors such as swarming, pyocyanin production, and secretion of the ExoU toxin via the type III secretion system (T3SS). Five of the seven extracts with the best anti-pathogenic activity reduced ExoU secretion, and the extracts of Diphysa americana and Hibiscus sabdariffa were identified as the most active. Therefore, the abscess/necrosis model allows identification of plant extracts that have the capacity to reduce pathogenicity of P. aeruginosa. Furthermore, we evaluated the activity of the plant extracts on Chromobacterium violaceum. T3SS (ΔescU) and QS (ΔcviI) mutant strains were assessed in both the abscess/necrosis and sepsis models. Only the ΔescU strain had lower pathogenicity in the animal models, although no activity of plant extracts was observed. These results demonstrate differences between the anti-virulence activity recorded in vitro and pathogenicity in vivo and between the roles of QS and T3S systems as virulence determinants.
Highlights
Bacteria are social microorganisms that use quorum sensing (QS) to communicate and induce multicellular behaviors [1]
We have recently identified hibiscus acid isolated from Hibiscus sabdariffa as a compound with anti-pathogenic activity using the abscess/necrosis model [19]
We identify plant extracts that reduce the pathogenicity of P. aeruginosa at sub-inhibitory concentrations and others that stimulate it
Summary
Bacteria are social microorganisms that use quorum sensing (QS) to communicate and induce multicellular behaviors [1]. QS is dependent on cell density and is a mechanism by which bacteria release chemical signals (called autoinducers) to their microenvironment to perceive the presence of other cells [2]. This phenomenon allows bacteria to regulate expression of genes that control production of various metabolites and virulence factors, which is the reason it is considered an important target to block bacterial pathogenicity [3]. There are reports of phytochemicals with anti-virulence properties that reduce the pathogenicity of Pseudomonas aeruginosa in some animal models (Caenorhabditis elegans, Danio rerio, and Galleria mellonella), in the case of murine models, the reports are scarce [3,8]. In the case of phytochemicals, the prophylactic administration of synthetic ajoene [(E,Z)-4,5,9-trithiadodeca-1,6,11-triene 9 oxide]
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