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Effect of kitasamycin and nitrofurantoin at subinhibitory concentrations on quorum sensing regulated traits of Chromobacterium violaceum.
Antonie van Leeuwenhoek ( IF 1.8 ) Pub Date : 2020-09-05 , DOI: 10.1007/s10482-020-01467-6
Yasser Musa Ibrahim 1 , Ahmed Megahed Abouwarda 1 , Farghaly Abdelhamid Omar 2
Affiliation  

Quorum sensing (QS) is a mechanism of intercellular communication in bacteria that received substantial attention as alternate strategy for combating bacterial resistance and the development of new anti-infective agents. The present investigation reports on the assessment of using subinhibitory concentrations of antibiotics for the inhibition of QS-regulated phenotypes in Chromobacterium violaceum. Primarily, the minimum inhibitory concentrations of a series of antibiotics were determined by a microdilution method. Subsequently, the inhibitory effects of selected antibiotics on QS-regulated traits, namely violacein and chitinase production, biofilm formation and motility were evaluated using C. violaceum CV026 and C. violaceum ATCC 12472. Results revealed that kitasamycin and nitrofurantoin exhibited the highest quorum sensing inhibitory (QSI) activity. The amount of violacein produced by C. violaceum was significantly reduced in the presence of either kitasamycin or nitrofurantoin. Moreover, the chitinolytic activity, biofilm formation, and motility were also impaired in kitasamycin or nitrofurantoin-treated cultures. We further confirmed QSI effects at the molecular level using molecular docking and real-time quantitative polymerase chain reaction (RT-qPCR). Results of molecular docking suggested that both antibiotics can interact with CviR transcriptional regulator of C. violaceum. Furthermore, RT-qPCR revealed the suppressive effect of kitasamycin and nitrofurantoin on five genes under the control of the CviI/CviR system: cviI, cviR, vioB, vioC, and vioD. Giving that kitasamycin and nitrofurantoin are being safely used for decades, this study emphasizes their potential application as antivirulence agents to disarm resistant bacterial strains, making their removal an easier task for the immune system or for another antibacterial agent.



中文翻译:

亚抑制浓度的Kitasamycin和呋喃妥因对紫罗兰色杆菌的群体感应调控特性的影响。

群体感应(QS)是细菌中细胞间通讯的一种机制,作为对抗细菌耐药性和开发新抗感染剂的替代策略,受到了广泛关注。本研究报告评估使用亚抑制浓度的抗生素抑制紫癜杆菌中QS调节的表型。首先,通过微量稀释法确定一系列抗生素的最小抑菌浓度。随后,使用C. violaceum CV026和C. violaceum评价了所选抗生素对QS调节性状(即紫胶素和几丁质酶产生,生物膜形成和运动)的抑制作用ATCC12472。结果显示,Kitasamycin和呋喃妥因具有最高的群体感应抑制(QSI)活性。通过产生紫色杆菌素的量C.堇色在任一吉他霉素或呋喃妥因的存在下显著降低。此外,在卡他霉素或呋喃妥因处理的培养物中,几丁质分解活性,生物膜形成和运动性也受到损害。我们使用分子对接和实时定量聚合酶链反应(RT-qPCR)在分子水平进一步证实了QSI的作用。分子对接的结果表明,两种抗生素都可以与紫花衣藻的CviR转录调节因子相互作用。此外,RT-qPCR揭示了在CviI / CviR系统控制下的五个基因对Kitasamycin和nitrofurantoin的抑制作用:cviIcviRvioBvioCvioD。考虑到kitasamycin和nitrofurantoin已安全使用了数十年,这项研究强调了它们作为抗毒剂的潜在应用,可以解除耐药菌的武装,使它们的清除对于免疫系统或另一种抗菌剂而言更加容易。

更新日期:2020-09-07
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