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Inhibition of biofilm and virulence properties of Pseudomonas aeruginosa by sub-inhibitory concentrations of aminoglycosides.
Microbial Pathogenesis ( IF 3.3 ) Pub Date : 2020-05-11 , DOI: 10.1016/j.micpath.2020.104249
Fazlurrahman Khan 1 , Jang-Won Lee 2 , Aqib Javaid 3 , Seul-Ki Park 1 , Young-Mog Kim 4
Affiliation  

Aminoglycosides are a commonly used class of antibiotics; however, their application has been discontinued due to the emergence of multi-drug resistance bacterial strains. In the present study, the subinhibitory concentrations (sub-MIC) of several aminoglycosides were determined and tested as an antibiofilm and for their anti-virulence properties against Pseudomonas aeruginosa PAO1, which is an opportunistic foodborne pathogen. P. aeruginosa PAO1 exhibits multiple mechanisms of resistance, including the formation of biofilm and production of several virulence factors, against aminoglycoside antibiotics. The sub-MIC of these antibiotics exhibited biofilm inhibition of P. aeruginosa in alkaline TSB (pH 7.9). Moreover, various concentrations of these aminoglycosides also eradicate the mature biofilm of P. aeruginosa. In the presence of sub-MIC of aminoglycosides, the morphological changes of P. aeruginosa were found to change from rod-shaped to the filamentous, elongated, and streptococcal forms. Similar growth conditions and sub-MIC of aminoglycosides were also found to attenuate several virulence properties of P. aeruginosa PAO1. Molecular docking studies demonstrate that these aminoglycosides possess strong binding properties with the LasR protein, which is a well-characterized quorum-sensing receptor of P. aeruginosa. The present study suggests a new approach to revitalize aminoglycosides as antibiofilm and antivirulence drugs to treat infections caused by pathogenic bacteria.

中文翻译:

通过亚抑制浓度的氨基糖苷类抑制铜绿假单胞菌的生物膜和毒力特性。

氨基糖苷是常用的一类抗生素。然而,由于出现了多药耐药性细菌菌株,它们的应用已被中止。在本研究中,确定了几种氨基糖苷的亚抑制浓度(sub-MIC),并作为抗生物膜进行了测试,并测试了它们对铜绿假单胞菌PAO1(一种机会性食源性病原体)的抗毒特性。铜绿假单胞菌PAO1表现出多种抗药性,包括对氨基糖苷类抗生素的生物膜形成和几种毒力因子的产生。这些抗生素的亚MIC在碱性TSB(pH 7.9)中表现出对铜绿假单胞菌的生物膜抑制作用。而且,这些氨基糖苷的各种浓度也消除了铜绿假单胞菌的成熟生物膜。在氨基糖苷的亚MIC存在下,发现铜绿假单胞菌的形态学变化从杆状变为丝状,细长和链球菌形式。还发现相似的生长条件和氨基糖苷的亚MIC减弱了铜绿假单胞菌PAO1的几种毒力特性。分子对接研究表明,这些氨基糖苷类与LasR蛋白具有很强的结合特性,而LasR蛋白是铜绿假单胞菌的群体感应受体。本研究提出了一种新的方法来活化氨基糖苷作为抗生物膜和抗毒性药物,以治疗由病原菌引起的感染。还发现相似的生长条件和氨基糖苷的亚MIC减弱了铜绿假单胞菌PAO1的几种毒力特性。分子对接研究表明,这些氨基糖苷类与LasR蛋白具有很强的结合特性,而LasR蛋白是铜绿假单胞菌的群体感应受体。本研究提出了一种新的方法来活化氨基糖苷作为抗生物膜和抗毒药,以治疗由病原菌引起的感染。还发现相似的生长条件和氨基糖苷的亚MIC减弱了铜绿假单胞菌PAO1的几种毒力特性。分子对接研究表明,这些氨基糖苷类与LasR蛋白具有很强的结合特性,而LasR蛋白是铜绿假单胞菌的群体感应受体。本研究提出了一种新的方法来活化氨基糖苷作为抗生物膜和抗毒药,以治疗由病原菌引起的感染。
更新日期:2020-05-11
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