Attenuation of Pseudomonas aeruginosa quorum sensing, virulence and biofilm formation by extracts of Andrographis paniculata
Attenuation of Pseudomonas aeruginosa quorum sensing, virulence and biofilm formation by extracts of Andrographis paniculata
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DOI：
10.1016/j.micpath.2017.10.023
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发表时间：
2017-12-01
影响因子：
3.8
通讯作者：
Mukherjee, Samir Kumar
中科院分区：
文献类型：
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作者：
Banerjee, Malabika;Moulick, Soumitra;Mukherjee, Samir Kumar
已知群体感应（QS）在铜绿假单胞菌感染期间的毒力因子和毒素调节中发挥重要作用，这可能经常导致抗生素耐药性和炎症性损伤的不良结果。因此，迫切需要寻找一种既能靶向QS又能预防炎症损伤的低耐药风险的新型药物。穿心莲（Andrographis paniculata）是穿心莲科的一种草本植物，原产于亚洲国家，也在斯堪的纳维亚半岛和欧洲的一些地区种植，具有很强的传统用途，具有抗菌、消炎、解热、抗病毒和抗氧化的特性。本研究以三氯甲烷、甲醇和水为溶剂，考察了三种不同溶剂提取物的抗qs和抗炎活性。采用Real - Time-PCR技术，在转录水平上研究了对部分qs调控基因的影响。此外，研究人员还对铜绿假单胞菌感染后MAPK通路的衰减能力进行了研究，以检验其潜在的抗炎活性。氯仿和甲醇提取物显著降低了铜绿假单胞菌胞外毒力因子（pyocyanin, elastase, total protease，鼠李糖脂和溶血素）的表达（p < 0.05），但不影响细菌活力。它们还显著（p < 0.05）降低了铜绿假单胞菌的蜂群运动和生物膜的形成。氯仿提取物对Iasi、lasR、rhll和rhlR的表达分别降低61%、75%、41%和44%，效果更好。此外，氯仿提取物降低了铜绿假单胞菌感染巨噬细胞MAPK信号通路中p-p38和p-ERK1/2的表达水平。本研究表明，金针叶提取物对铜绿假单胞菌的QS有抑制作用，并具有抗炎活性，有望成为铜绿假单胞菌感染的治疗药物。
Quorum-sensing (QS) is known to play an essential role in regulation of virulence factors and toxins during Pseudomonas aeruginosa infection which may frequently cause antibiotic resistance and hostile outcomes of inflammatory injury. Therefore, it is an urgent need to search for a novel agent with low risk of resistance development that can target QS and inflammatory damage prevention as well. Andrographis paniculata, a herbaceous plant under the family Acanthaceae, native to Asian countries and also cultivated in Scandinavia and some parts of Europe, has a strong traditional usage with its known antibacterial, anti-inflammatory, antipyretic, antiviral and antioxidant properties. In this study, three different solvent extracts (viz., chloroform, methanol and aqueous) of A. paniculata were examined for their anti-QS and anti-inflammatory activities. Study was carried out to assess the effect on some selected QS-regulatory genes at transcriptional level using Real Time-PCR. In addition, ability to attenuate MAPK pathways upon P. aeruginosa infection was performed to check its potential anti-inflammatory activity. Chloroform and methanol extracts showed significant reduction (p < 0.05) of the QS-controlled extracellular virulence factors in P. aeruginosa including the expression of pyocyanin, elastase, total protease, rhamnolipid and hemolysin without affecting bacterial viability. They also significantly (p < 0.05) reduced swarming motility and biofilm formation of P. aeruginosa. The chloroform extract, which was found to be more effective, decreased expression of Iasi, lasR, rhll and rhlR by 61%, 75%, 41%, and 44%, respectively. Moreover, chloroform extract decreased activation of p-p38 and p-ERK1/2 expression levels in MAPK signal pathways in P. aeruginosa infected macrophage cells. As the present study demonstrates that A. paniculata extracts inhibit QS in P. aeruginosa and exhibit anti-inflammatory activities, therefore it represents itself as a prospective therapeutic agent against P. aeruginosa infection.