Bendary Mahmoud M, Ali Mohamed A M, Abdel Halim Alyaa S, Boufahja Fehmi, Chaudhary Anis Ahmad, Elkelish Amr, Soliman Rania H M, Hegazy Wael A H
Department of Microbiology and Immunology, Faculty of Pharmacy, Port Said University, Port Said, Egypt.
Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia.
Front Pharmacol. 2024 May 21;15:1406653. doi: 10.3389/fphar.2024.1406653. eCollection 2024.
, a significant bacterium, can cause severe illness and resistance to antibiotics. Quorum sensing (QS) systems regulate virulence factors production. Targeting QS could reduce bacteria pathogenicity and prevent antibiotic resistance. Cruciferous vegetables contain sulforaphane, known for its anti-inflammatory, antioxidant, anticancer, and antimicrobial properties.
We aimed to examine the inhibitory influences of sulforaphane, at a sub-inhibitory concentration (¼ minimum inhibitory concentration, MIC), on virulence and QS in .
The sulforaphane's anti-virulence actions at sub-inhibitory concentrations were explored and . A sub-MIC concentration of sulforaphane was combined with anti-pseudomonal drugs, and the results of this combination were assessed. The virtual affinity of sulforaphane for the receptors of QS was studied, and its effect on the expression of QS genes was quantified.
Sulforaphane significantly decreased the biofilm formation, motility, ability to withstand oxidative stress, and the synthesis of virulence extracellular enzymes such as proteases, hemolysins, and elastase, as well as other virulence factors like pyocyanin. In addition, sulforaphane lessened the severity of infection in mice. Sulforaphane reduced the antipseudomonal antibiotics' MICs when used together, resulting in synergistic effects. The observed anti-virulence impacts were attributed to the ability of sulforaphane to inhibit QS via suppressing the QS genes' expression.
Sulforaphane shows promise as a potent anti-virulence and anti-QS agent that can be used alongside conventional antimicrobials to manage severe infections effectively. Furthermore, this study paves the way for further investigation of sulforaphane and similar structures as pharmacophores for anti-QS candidates.
[细菌名称]是一种重要细菌,可导致严重疾病并产生抗生素耐药性。群体感应(QS)系统调控毒力因子的产生。靶向群体感应可降低细菌致病性并预防抗生素耐药性。十字花科蔬菜含有萝卜硫素,以其抗炎、抗氧化、抗癌和抗菌特性而闻名。
我们旨在研究亚抑制浓度(¼最低抑菌浓度,MIC)的萝卜硫素对[细菌名称]毒力和群体感应的抑制作用。
研究了亚抑制浓度下萝卜硫素的抗毒力作用[具体研究方法]。将亚MIC浓度的萝卜硫素与抗铜绿假单胞菌药物联合使用,并评估这种联合的效果。研究了萝卜硫素与群体感应受体的虚拟亲和力,并对其对群体感应基因表达的影响进行了定量分析。
萝卜硫素显著降低了生物膜形成、运动性、抗氧化应激能力以及蛋白酶、溶血素和弹性蛋白酶等毒力细胞外酶的合成,以及绿脓菌素等其他毒力因子。此外,萝卜硫素减轻了小鼠[细菌名称]感染的严重程度。萝卜硫素与抗铜绿假单胞菌抗生素联合使用时降低了其MIC,产生协同效应。观察到的抗毒力影响归因于萝卜硫素通过抑制群体感应基因表达来抑制群体感应的能力。
萝卜硫素有望成为一种有效的抗毒力和抗群体感应剂,可与传统抗菌药物联合使用以有效管理严重感染。此外,本研究为进一步研究萝卜硫素及类似结构作为抗群体感应候选药物的药效基团铺平了道路。