Effect of kitasamycin and nitrofurantoin at subinhibitory concentrations on quorum sensing regulated traits of Chromobac
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ORIGINAL PAPER
Effect of kitasamycin and nitrofurantoin at subinhibitory concentrations on quorum sensing regulated traits of Chromobacterium violaceum Yasser Musa Ibrahim
. Ahmed Megahed Abouwarda
. Farghaly Abdelhamid Omar
Received: 11 July 2020 / Accepted: 25 August 2020 Ó Springer Nature Switzerland AG 2020
Abstract 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. Keywords Antibiofim Chromobacterium violaceum Kitasamycin Molecular docking Nitrofurantoin Quorum sensing inhibitors
Introduction Y. M. Ibrahim (&) A. M. Abouwarda Department of Microbiology, General Division of Basic Medical Sciences, National Organization for Drug Control and Research (NODCAR), Giza 12611, Egypt e-mail: [email protected] F. A. Omar Department of Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt
Antibiotic resistance has become a global threat to public health systems and considered to be a leading health challenge in recent years (Ferri et al. 2017). Application of novel strategies which could control bacterial pathogenesis in order to tackle multidrug resistant (MDR) pathogens is therefore becoming a
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