Secnidazole Is a Promising Imidazole Mitigator of Serratia marcescens Virulence

Abstract

<i>Serratia marcescens</i> is an opportunistic pathogen that causes diverse nosocomial infections. <i>S. marcescens</i> has developed considerable resistance to different antibiotics and is equipped with an armory of virulence factors. These virulence factors are regulated in <i>S. marcescens</i> by an intercellular communication system termed quorum sensing (QS). Targeting bacterial virulence and QS is an interesting approach to mitigating bacterial pathogenesis and overcoming the development of resistance to antimicrobials. In this study, we aimed to evaluate the anti-virulence activities of secnidazole on a clinical isolate of <i>S. marcescens</i>. The effects of secnidazole at sub-inhibitory concentrations (sub-MICs) on virulence factors, swarming motility, biofilm formation, proteases, hemolysin activity, and prodigiosin production were evaluated in vitro. Secnidazole's protective activity against <i>S. marcescens</i> pathogenesis was assessed in vivo in mice. Furthermore, a molecular docking study was conducted to evaluate the binding ability of secnidazole to the <i>S. marcescens</i> SmaR QS receptor. Our findings showed that secnidazole at sub-MICs significantly reduced <i>S. marcescens</i> virulence factor production in vitro and diminished its pathogenesis in mice. The <i>insilico</i> docking study revealed a great ability of secnidazole to competitively hinder the binding of the autoinducer to the SmaR QS receptor. In conclusion, secnidazole is a promising anti-virulence agent that may be used to control infections caused by <i>S. marcescens</i>.