The main goal of this study was to evaluate the inhibition of Pseudomonas aeruginosa virulence factors and Quorum Sensing during exposure to carvacrol. P. aeruginosa (ATCC 10154) was exposed to carvacrol determining changes in biofilm development, motility, acyl-homoserine lactones (AHL) synthesis and relative expression of lasI/lasR. Docking analysis was used to determinate interactions between carvacrol with LasI and LasR proteins. P. aeruginosa produced 60% lower AHLs when exposed to carvacrol (1.9 mM) compared to control, without affecting cellular viability, indicating a reduction on the LasI synthase activity. AHL-C12, C6, and C4 were detected and related to biofilm development, motility, and pyocyanin production, respectively. The presence of carvacrol reduced the expression of lasR, without affecting lasI gen. Moreover, computational docking showed interactions of carvacrol with amino acids in the active site pocket of LasI (−5.6 kcal mol⁻¹) and within the binding pocket of LasR (−6.7 kcal mol⁻¹) of P. aeruginosa. These results demonstrated that virulence of P. aeruginosa was reduced by carvacrol, by inhibiting LasI activity with the concomitant reduction on the expression of lasR, biofilm and swarming motility. This study provides relevant information about the effect of carvacrol against quorum sensing to inhibit virulence factors of P. aeruginosa at enzymatic and gene levels. These findings can contribute to the development of natural anti-QS products, which can affect pathogenesis.

中文翻译：

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暴露于香芹酚的铜绿假单胞菌的毒力：酶和基因水平上群体感应的改变。

本研究的主要目的是评估在香芹酚暴露期间对铜绿假单胞菌毒力因子和群体感应的抑制作用。铜绿假单胞菌(ATCC 10154) 暴露于香芹酚，决定了生物膜发育、运动、酰基高丝氨酸内酯 (AHL) 合成和lasI/lasR相对表达的变化。对接分析用于确定香芹酚与 LasI 和 LasR 蛋白之间的相互作用。铜绿假单胞菌与对照相比，当暴露于香芹酚 (1.9 mM) 时产生的 AHL 降低 60%，而不影响细胞活力，表明 LasI 合酶活性降低。检测到 AHL-C12、C6 和 C4 并分别与生物膜发育、运动和绿脓素产生有关。香芹酚的存在降低了lasR的表达，而不影响lasI gen。此外，计算对接显示香芹酚与铜绿假单胞菌LasI 活性位点口袋 (-5.6 kcal mol ^-1 ) 和 LasR 结合口袋 (-6.7 kcal mol ^-1 ) 中的氨基酸相互作用。这些结果表明，铜绿假单胞菌的毒力香芹酚通过抑制 LasI 活性，同时降低lasR、生物膜和蜂群运动性的表达，从而减少 。本研究提供了有关香芹酚对群体感应抑制铜绿假单胞菌毒力因子在酶和基因水平上的作用的相关信息。这些发现有助于开发可能影响发病机制的天然抗 QS 产品。