Inhibition of Microbial Quorum Sensing Mediated Virulence Factors by Pestalotiopsis sydowiana.
Inhibition of Microbial Quorum Sensing Mediated Virulence Factors by Pestalotiopsis sydowiana.
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DOI：
10.4014/jmb.1907.07030
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发表时间：
2020-04-28
影响因子：
2.8
通讯作者：
Siddhardha B
中科院分区：
文献类型：
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作者：
Parasuraman P;Devadatha B;Sarma VV;Ranganathan S;Ampasala DR;Reddy D;Kumavath R;Kim IW;Patel SKS;Kalia VC;Lee JK;Siddhardha B
群体感应（QS）介导的感染导致人类严重疾病。通过使用抗病原体药物抑制QS来控制传染病是一种有前途的方法，因为抗生素在治疗这些疾病中被证明是无效的。海洋真菌Pestalotiopsis sydowiana PPR提取物具有较强的抗病原菌活性。真菌提取物对测试病原体铜绿假单胞菌PAO 1的最小抑菌浓度（MIC）为1，000 μg/ml。亚MIC浓度（250和500 μg/ml）的真菌提取物使铜绿假单胞菌PAO 1中QS调节的毒力表型（如绿脓菌素、几丁质酶、蛋白酶、弹性蛋白酶的产生和葡萄球菌溶解活性）分别降低84.15%、73.15%、67.37%、62.37%和33.65%。此外，它还减少了胞外多糖（74.99%），鼠李糖脂（68.01%）和海藻酸盐（54.98%）的产生，并抑制细菌的生物膜形成90.54%。计算机模拟分析显示，聚原草PPR的代谢产物与细菌QS受体蛋白（LasR和RhlR）结合，类似于其各自的天然信号分子。环（-Leu-Pro）（CLP）和4-羟基苯乙酰胺（4-HPA）是通过计算机模拟方法鉴定出的具有生物活性的化合物。CLP和4-HPA对铜绿假单胞菌PAO 1的MIC值分别为250和125 μg/ml。在亚MIC浓度下，CLP（125 μg/ml）和4-HPA（62.5 μg/ml）均能显著降低所有毒力因子。基因表达研究进一步证实了这一点。研究结果表明，P. sydowiana PPR的代谢产物可以作为有前途的QS抑制剂，针对病原菌。
Quorum sensing (QS)-mediated infections cause severe diseases in human beings. The control of infectious diseases by inhibiting QS using antipathogenic drugs is a promising approach as antibiotics are proving inefficient in treating these diseases. Marine fungal (Pestalotiopsis sydowiana PPR) extract was found to possess effective antipathogenic characteristics. The minimum inhibitory concentration (MIC) of the fungal extract against test pathogen Pseudomonas aeruginosa PAO1 was 1,000 μg/ml. Sub-MIC concentrations (250 and 500 μg/ml) of fungal extract reduced QS-regulated virulence phenotypes such as the production of pyocyanin, chitinase, protease, elastase, and staphylolytic activity in P. aeruginosa PAO1 by 84.15%, 73.15%, 67.37%, 62.37%, and 33.65%, respectively. Moreover, it also reduced the production of exopolysaccharides (74.99%), rhamnolipids (68.01%), and alginate (54.98%), and inhibited the biofilm formation of the bacteria by 90.54%. In silico analysis revealed that the metabolite of P. sydowiana PPR binds to the bacterial QS receptor proteins (LasR and RhlR) similar to their respective natural signaling molecules. Cyclo(-Leu-Pro) (CLP) and 4-Hydroxyphenylacetamide (4-HPA) were identified as potent bioactive compounds among the metabolites of P. sydowiana PPR using in silico approaches. The MIC values of CLP and 4-HPA against P. aeruginosa PAO1 were determined as 250 and 125 μg/ml, respectively. All the antivirulence assays were conducted at sub-MIC concentrations of CLP (125 μg/ml) and 4-HPA (62.5 μg/ml), which resulted in marked reduction in all the investigated virulence factors. This was further supported by gene expression studies. The findings suggest that the metabolites of P. sydowiana PPR can be employed as promising QS inhibitors that target pathogenic bacteria.