Ambroxol interferes with Pseudomonas aeruginosa quorum sensing.
Ambroxol interferes with Pseudomonas aeruginosa quorum sensing.
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DOI：
10.1016/j.ijantimicag.2010.05.007
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发表时间：
2010-09
影响因子：
10.8
通讯作者：
Qi Lu;Jialin Yu;Xi-qiang Yang;Jiarong Wang;Li-jia Wang;Ya-yin Lin;Lihua Lin
中科院分区：
文献类型：
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作者：
Qi Lu;Jialin Yu;Xi-qiang Yang;Jiarong Wang;Li-jia Wang;Ya-yin Lin;Lihua Lin
据报道，黏液溶解剂氨溴索除了减少海藻酸盐的产生外，还能干扰铜绿假单胞菌衍生的生物膜的形成，其机制尚不明确。由于群体感应是毒力和生物膜形成的关键调节因子，我们研究了氨溴索对铜绿假单胞菌PAO1野生型细菌清除率、粘附谱和生物膜形成的影响，并与群体感应缺陷、双突变菌株ΔlasR ΔrhlR和ΔlasI ΔrhlI进行了比较。本报告中的数据表明，与野生型菌株相比，氨溴索处理以剂量依赖的方式降低了双突变菌株的存活率，尽管双突变菌株在氨溴索的存在下比野生型菌株具有更高的粘附性。与ΔlasR ΔrhlR（7.36±0.2μm）和ΔlasI ΔrhlI（6.62±0.31μm）菌株相比，PAO1野生型菌株的生物膜厚度（21.64±0.57μm）显著增加。氨溴索处理降低了野生型和双突变菌株的生物膜厚度，增加了面积孔隙度，降低了平均扩散距离和文本熵。然而，与双突变菌株相比，野生型菌株的变化更为明确。最后，氨溴索表现出显著的拮抗群体感应特性，这表明它可以用于临床治疗囊性纤维化，减少生物膜的形成和留置装置的定植。
The mucolytic agent ambroxol has been reported to interfere with the formation of Pseudomonas aeruginosa-derived biofilms in addition to reducing alginate production by undefined mechanisms. Since quorum sensing is a key regulator of virulence and biofilm formation, we examined the effects of ambroxol on P. aeruginosa PAO1 wild-type bacterial clearance rates, adhesion profiles and biofilm formation compared with the quorum sensing-deficient, double-mutant strains ΔlasR ΔrhlR and ΔlasI ΔrhlI. Data presented in this report demonstrated that ambroxol treatment reduced survival rates of the double-mutant strains compared with the wild-type strain in a dose-dependent manner even though the double-mutants had increased adhesion in the presence of ambroxol compared with the wild-type strain. The PAO1 wild-type strain produced a significantly thicker biofilm (21.64±0.57μm) compared with the biofilms produced by the ΔlasR ΔrhlR (7.36±0.2μm) and ΔlasI ΔrhlI (6.62±0.31μm) isolates. Ambroxol treatment reduced biofilm thickness, increased areal porosity, and decreased the average diffusion distance and textual entropy of wild-type and double-mutant strains. However, compared with the double-mutant strains, the changes observed for the wild-type strain were more clearly defined. Finally, ambroxol exhibited significant antagonistic quorum-sensing properties, suggesting that it could be adapted for use clinically in the treatment of cystic fibrosis and to reduce biofilm formation and in the colonisation of indwelling devices.