Quorum quelling efficacy of marine cyclic dipeptide -cyclo(L-leucyl-L-prolyl) against the uropathogen Serratia marcescens

Food Chem Toxicol. 2019 Jan:123:326-336. doi: 10.1016/j.fct.2018.11.013. Epub 2018 Nov 9.

Abstract

In the current study, the anti-quorum sensing (QS) efficacy of cyclic dipeptide -cyclo(L-leucyl-L-prolyl) (CLP) of marine origin was explored against Serratia marcescens. Minimal -inhibitory (MIC) and -bactericidal concentrations (MBC) of CLP against both reference as well as a clinical isolate of S. marcescens was identified to be 200 and 400 µg/mL, respectively. CLP proficiently inhibited the QS controlled prodigiosin production in S. marcescens, which affirm its anti-QS efficacy towards S. marcescens. At sub-MIC (100 µg/mL), CLP exhibited a phenomenal inhibitory propensity towards the production of virulence traits viz. biofilm, exopolymeric substance, protease and lipase to the level of 81, 77, 71 and 92%, respectively. Further, the confocal and scanning electron microscopic analyses validated the antibiofilm efficacy of CLP. Besides, CLP effectively modified the hydrophobic and motility characteristics of S. marcescens. Furthermore, the in vivo assay using C. elegans revealed the non-toxic and anti-adherence propensity of CLP. Concomitantly, the down regulation of QS controlled virulence genes (unveiled through qPCR analysis) are in accordance with the data of phenotypic and in vivo assays. Therefore, this study exemplifies that CLP could plausibly be a convincing alternative over conventional antibiotics in preventing the QS associated pathogenesis of uropathogens.

Keywords: Confocal laser scanning microscopy; Cyclic dipeptide; Exopolymeric substances; Quorum sensing; Scanning electron microscopy; Urinary tract infections.

MeSH terms

  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Biofilms / drug effects
  • Caenorhabditis elegans
  • Dipeptides / pharmacology*
  • Humans
  • Microbial Sensitivity Tests
  • Quorum Sensing / drug effects*
  • Serratia Infections / microbiology*
  • Serratia marcescens / drug effects*
  • Serratia marcescens / genetics
  • Serratia marcescens / pathogenicity
  • Serratia marcescens / physiology
  • Urinary Tract Infections / microbiology*
  • Virulence / drug effects

Substances

  • Bacterial Proteins
  • Dipeptides