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Evaluating the effect of antibiotics sub-inhibitory dose on Pseudomonas aeruginosa quorum sensing dependent virulence and its phenotypes
Saudi Journal of Biological Sciences Pub Date : 2020-10-28 , DOI: 10.1016/j.sjbs.2020.10.040
Fadilah Sfouq Aleanizy , Fulwah Y. Alqahtani , Esra Kamal Eltayb , Norah Alrumikan , Renad Almebki , Abdulaziz Alhossan , Thamer A. Almangour , Hajar AlQahtani

The opportunistic Pseudomonas aeruginosa virulence controlled by quorum sensing (QS) also identified as, cell-cell communication. QS system is organized by the LasI-LasR and the RhlI-RhlR components. Provided that QS tends to perform a key role in virulence gene expression and host defence function, QS inhibitors have been proposed as potential antipseudomonal therapies. Sub-inhibitory concentrations (sub-MIC) of antibiotics, although having biostatic effect on bacteria, but can interfere with bacterial QS system and virulence. This research aimed to examine the impact of sub-MIC of azithromycin, imipenem, cefepime and piperacillin/tazobactam on the QS-dependent virulence including pyocyanin and biofilm production, haemolysin, protease and DNase in P. aeruginosa wildtype and mutant strains; transcriptional-regulator (ΔLasR), autoinducer synthesis protein (ΔLasI), transcriptional-regulator (ΔRhlR), protease precursor (ΔLasA) and double regulators mutants (ΔLasR/RhlR). The growth of all strains showed similar pattern, however, in presence of antibiotics significant growth variation was observed among mutant strains when compared to wild type strain. Antimicrobial activity tested by agar diffusion method of all antibiotics on all strains were used to compare the zones of therapeutic and sub-MIC doses showing a significant difference in the inhibition zone. QS-dependant virulence as biofilm, pyocyanin, protease, haemolysin and DNase production showed significant variation on all strains compared to wild type in response to antibiotics used at sub-MIC doses. In conclusion well known antibiotics can be used in sub-MIC doses to decrease the virulence of P. aeruginosa in addition to overcoming the major side effect of the high doses and the occurrence of resistance.



中文翻译:

评价抗生素亚抑制剂量对铜绿假单胞菌 群体感应依赖性毒力及其表型的影响

由群体感应(QS)控制的机会性铜绿假单胞菌毒力也被确定为细胞间通讯。QS系统由LasI-LasR和RhlI-RhlR组件组织。如果QS倾向于在毒力基因表达和宿主防御功能中起关键作用,则QS抑制剂已被提议作为潜在的抗假性伪狂犬病疗法。抗生素的亚抑制浓度(sub-MIC)虽然对细菌具有生物抑制作用,但会干扰细菌QS系统和毒力。这项研究旨在检查阿奇霉素,亚胺培南,头孢吡肟和哌拉西林/他唑巴坦的亚MIC对QS依赖性毒力的影响,包括绿脓杆菌和生物膜的产生,溶血素,蛋白酶和DNase 野生型和突变株;转录调节因子(ΔLasR),自诱导合成蛋白(ΔLasI),转录调节因子(ΔRhlR),蛋白酶前体(ΔLasA)和双重调节突变体(ΔLasR/ RhlR)。所有菌株的生长均显示出相似的模式,但是,与野生型菌株相比,在存在抗生素的情况下,突变菌株之间观察到了显着的生长变化。通过琼脂扩散法对所有菌株进行的所有抗生素的琼脂扩散法测试的抗菌活性用于比较治疗剂量和亚MIC剂量的区域,这些区域在抑制区域上显示出显着差异。QS依赖的毒力如生物膜,绿脓素,蛋白酶,溶血素和DNase的生产表现出响应于低于MIC剂量使用的抗生素,与野生型相比,所有菌株均具有显着差异。铜绿假单胞菌除了克服了高剂量的主要副作用和耐药性的发生。

更新日期:2020-12-25
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