Cyclic dipeptide cyclo(l-leucyl-l-prolyl) from marine Bacillus amyloliquefaciens mitigates biofilm formation and virulence in Listeria monocytogenes

Abstract

This study was intentionally focused on cyclo(l-leucyl-l-prolyl) (CLP), a cyclic dipeptide with myriad pharmaceutical significance, to explore its antivirulence efficacy against the predominant foodborne pathogen,Listeria monocytogenes(LM). Minimum inhibitory concentration (MIC) of CLP against LM ATCC 19111 was found to be 512 μg mL(-1) CLP at sub-MICs (64 128, 256 μg mL(-1)) demonstrated a profound non-bactericidal dose-dependent antibiofilm efficacy (on polystyrene and glass) against LM, which was further confirmed through confocal and scanning electron microscopic analysis (on stainless steel surface).In vitrobioassays divulged the phenomenal inhibitory efficacy of CLP towards various virulence traits of LM, specifically its overwhelming suppression of swimming and swarming motility. Data ofin vivoassay usingCaenorhabditis eleganssignified that the plausible mechanism of CLP could be by impeding the pathogen's initial adhesion and thereby attenuating the biofilm assemblage and its associated virulence. This was further confirmed by significant decrease in extracellular polymeric substance, autoaggregation, hydrophobicity index and extracellular DNA of the CLP-treated LM cells. Collectively, this study unveils the antivirulence efficacy of CLP against the Gram-positive foodborne pathogen and the strainBacillus amyloliquefaciensaugurs well to be a promising probiotic in controlling infections associated with LM.