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Siphonocholin isolated from red sea sponge Siphonochalina siphonella attenuates quorum sensing controlled virulence and biofilm formation
Saudi Pharmaceutical Journal ( IF 3.0 ) Pub Date : 2020-09-12 , DOI: 10.1016/j.jsps.2020.09.002
Perwez Alam 1 , Ali S Alqahtani 1 , Fohad Mabood Husain 2 , Md Tabish Rehman 1 , Mohamed F Alajmi 1 , Omar M Noman 1 , Ali A El Gamal 1 , Shaza M Al-Massarani 1 , Mohammad Shavez Khan 3
Affiliation  

Increasing incidence of multi-drug resistant bacterial pathogens, especially in clinical settings, has been developed into a grave health situation. The drug resistance problem demands the necessity for alternative unique therapeutic policies. One such tactic is targeting the quorum sensing (QS) controlled virulence and biofilm production. In this study, we evaluated a marine steroid Siphonocholin (Syph-1) isolated from Siphonochalina siphonella against Chromobacterium violaceum (CV) 12472, Pseudomonas aeruginosa (PAO1), Methicillin-resistant Staphylococcus aureus (MRSA) and Acinetobacter baumannii (BAA) for biofilm and pellicle formation inhibition, and anti-QS property. MIC of Syph-1 against MRSA, CV, PAO1 was found as 64 µg/mL and 256 µg/mL against BAA. At selected sub-MICs, Syph-1 significantly (P ≤ 0.05) decreased the production of QS regulated virulence functions of CV12472 (violacein) and PAO1 [elastase, total protease, pyocyanin, chitinase, exopolysaccharides, and swarming motility]. The Syph-1 significantly decreased (p = 0.005) biofilm formation ability of tested bacterial pathogens, at sub-MIC level (PAO1 > MRSA > CV > BAA) and pellicle formation in A. baumannii (at 128 µg/mL). Molecular docking and simulation results indicated that Siph-1 was bound at the active site of BfmR N-terminal domain with high affinity. This study highlights the anti-QS and anti-biofilm activity of Syph-1 against bacterial pathogens reflecting its broad spectrum anti-infective potential.



中文翻译:


从红海海绵 Siphonochalina siphonella 中分离出的 Siphonocholin 可减弱群体感应控制的毒力和生物膜形成



多重耐药细菌病原体的发病率不断增加,特别是在临床环境中,已发展成为严重的健康状况。耐药性问题要求有必要采取替代的独特治疗政策。其中一种策略是针对群体感应(QS)控制的毒力和生物膜的产生。在这项研究中,我们评估了从Siphonochalina siphonella 中分离出的海洋类固醇 Siphonocholin (Syph-1) 对抗紫色色杆菌(CV) 12472、铜绿假单胞菌(PAO1)、耐甲氧西林金黄色葡萄球菌(MRSA) 和鲍曼不动杆菌(BAA) 的生物膜和抑制薄膜形成和抗 QS 特性。 Syph-1 对 MRSA、CV、PAO1 的 MIC 为 64 µg/mL,对 BAA 的 MIC 为 256 µg/mL。在选定的亚 MIC 中,Syph-1 显着 (P ≤ 0.05) 降低了 CV12472(紫罗兰素)和 PAO1 [弹性蛋白酶、总蛋白酶、绿脓素、几丁质酶、胞外多糖和蜂群运动] 的 QS 调节毒力功能的产生。 Syph-1 在亚 MIC 水平 (PAO1 > MRSA > CV > BAA) 显着降低 (p = 0.005) 测试细菌病原体的生物膜形成能力和鲍曼不动杆菌中的表膜形成能力(128 µg/mL) 。分子对接和模拟结果表明,Siph-1以高亲和力结合在BfmR N端结构域的活性位点上。这项研究强调了 Syph-1 对细菌病原体的抗 QS 和抗生物膜活性,反映了其广谱抗感染潜力。

更新日期:2020-11-17
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