Frikha Fakher, Jardak Marwa, Aifa Sami, Mnif Sami
Laboratory of Molecular and Cellular Screening Processes, Centre of Biotechnology of Sfax, University of Sfax, P O Box 1177, Sidi Mansour Road, 3018, Sfax, Tunisia.
Laboratory of Molecular and Cellular Screening Processes, Centre of Biotechnology of Sfax, University of Sfax, P O Box 1177, Sidi Mansour Road, 3018, Sfax, Tunisia.
Microb Pathog. 2024 Apr;189:106576. doi: 10.1016/j.micpath.2024.106576. Epub 2024 Feb 20.
Serratia marcescens is commonly noted to be an opportunistic pathogen and is often associated with nosocomial infections. In addition to its high antibiotic resistance, it exhibits a wide range of virulence factors that confer pathogenicity. Targeting quorum sensing (QS) presents a potential therapeutic strategy for treating bacterial infections caused by S. marcescens, as it regulates the expression of various virulence factors. Inhibiting QS can effectively neutralize S. marcescens' bacterial virulence without exerting stress on bacterial growth, facilitating bacterial eradication by the immune system. In this study, the antibacterial and anti-virulence properties of eugenol against Serratia sp. were investigated. Eugenol exhibited inhibitory effects on the growth of Serratia, with a minimal inhibitory concentration (MIC) value of 16.15 mM. At sub-inhibitory concentrations, eugenol also demonstrated antiadhesive and eradication activities by inhibiting biofilm formation. Furthermore, it reduced prodigiosin production and completely inhibited protease production. Additionally, eugenol effectively decreased swimming and swarming motilities in Serratia sp. This study demonstrated through molecular modeling, docking and molecular dynamic that eugenol inhibited biofilm formation and virulence factor production in Serratia by binding to the SmaR receptor and blocking the formation of the HSL-SmaR complex. The binding of eugenol to SmaR modulates biofilm formation and virulence factor production by Serratia sp. These findings highlight the potential of eugenol as a promising agent to combat S. marcescens infections by targeting its virulence factors through quorum sensing inhibition.
粘质沙雷氏菌通常被认为是一种机会致病菌,常与医院感染有关。除了具有高抗生素耐药性外,它还表现出多种赋予致病性的毒力因子。靶向群体感应(QS)为治疗由粘质沙雷氏菌引起的细菌感染提供了一种潜在的治疗策略,因为它调节各种毒力因子的表达。抑制群体感应可以有效中和粘质沙雷氏菌的细菌毒力,而不会对细菌生长施加压力,有利于免疫系统清除细菌。在本研究中,研究了丁香酚对沙雷氏菌属的抗菌和抗毒力特性。丁香酚对粘质沙雷氏菌的生长具有抑制作用,最低抑菌浓度(MIC)值为16.15 mM。在亚抑菌浓度下,丁香酚还通过抑制生物膜形成表现出抗粘附和清除活性。此外,它减少了灵菌红素的产生并完全抑制了蛋白酶的产生。此外,丁香酚有效地降低了粘质沙雷氏菌的游动和群集运动能力。本研究通过分子建模、对接和分子动力学证明,丁香酚通过与SmaR受体结合并阻断HSL-SmaR复合物的形成,抑制了粘质沙雷氏菌生物膜的形成和毒力因子的产生。丁香酚与SmaR的结合调节了粘质沙雷氏菌生物膜的形成和毒力因子的产生。这些发现突出了丁香酚作为一种有前景的药物的潜力,通过群体感应抑制靶向其毒力因子来对抗粘质沙雷氏菌感染。