Anti-Virulence Properties of Plant Species: Correlation between In Vitro Activity and Efficacy in a Murine Model of Bacterial Infection
2021
José Luis Díaz-Núñez | Macrina Pérez-López | Norma Espinosa | Nayelli Campos-Hernández | Rodolfo García-Contreras | Miguel Díaz-Guerrero | Humberto Cortes-López | Monserrat Vázquez-Sánchez | Héctor Quezada | Mariano Martínez-Vázquez | Ramón Marcos Soto-Hernández | Mireya Burgos-Hernández | Bertha González-Pedrajo | Israel Castillo-Juárez
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 <i>Pseudomonas aeruginosa</i> 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 <i>Diphysa americana</i> and <i>Hibiscus sabdariffa</i> were identified as the most active. Therefore, the abscess/necrosis model allows identification of plant extracts that have the capacity to reduce pathogenicity of <i>P. aeruginosa</i>. Furthermore, we evaluated the activity of the plant extracts on <i>Chromobacterium violaceum</i>. T3SS (Δ<i>escU</i>) and QS (Δ<i>cviI</i>) mutant strains were assessed in both the abscess/necrosis and sepsis models. Only the Δ<i>escU</i> 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.
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