Department of Microbiology, General Division of Basic Medical Sciences, National Organization for Drug Control and Research (NODCAR), Giza, 12611, Egypt.
Department of Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assiut, 71526, Egypt.
Antonie Van Leeuwenhoek. 2020 Nov;113(11):1601-1615. doi: 10.1007/s10482-020-01467-6. Epub 2020 Sep 5.
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.
群体感应（QS）是细菌细胞间通讯的一种机制，因其作为对抗细菌耐药性和开发新抗感染药物的替代策略而受到广泛关注。本研究报告了评估亚抑菌浓度抗生素抑制噬紫质菌中 QS 调节表型的情况。首先，通过微量稀释法确定了一系列抗生素的最小抑菌浓度。随后，使用噬紫质菌 CV026 和噬紫质菌 ATCC12472 评估了选定抗生素对 QS 调节特性（即紫质和几丁质酶的产生、生物膜形成和运动性）的抑制作用。结果表明，吉他霉素和呋喃妥因表现出最高的群体感应抑制（QSI）活性。吉他霉素或呋喃妥因的存在显著降低了噬紫质菌产生的紫质量。此外，几丁质酶活性、生物膜形成和运动性也在吉他霉素或呋喃妥因处理的培养物中受损。我们进一步通过分子对接和实时定量聚合酶链反应（RT-qPCR）在分子水平上证实了 QSI 效应。分子对接的结果表明，这两种抗生素都可以与噬紫质菌的 CviR 转录调节剂相互作用。此外，RT-qPCR 显示吉他霉素和呋喃妥因对 CviI/CviR 系统控制的五个基因（cviI、cviR、vioB、vioC 和 vioD）具有抑制作用。鉴于吉他霉素和呋喃妥因已安全使用数十年，本研究强调了它们作为抗毒剂的潜在应用，以解除耐药菌株的威胁，使免疫系统或另一种抗菌剂更容易清除它们。
