5-Dodecanolide inhibits biofilm formation and virulence of Streptococcus pyogenes by suppressing core regulons of virulence

Life Sci. 2020 Dec 1:262:118554. doi: 10.1016/j.lfs.2020.118554. Epub 2020 Oct 6.

Abstract

This study determined the antibiofilm and antivirulence potential of 5-Dodecanolide (DD) against an exclusive human pathogen Streptococcus pyogenes. Biofilm quantification assay showed antibiofilm efficacy of DD with maximum biofilm inhibition of 85% at 225 μg/mL concentration. Efficacy of antibacterial property of DD (225 μg/mL) was confirmed by CFU analysis and Alamar blue assay. Microscopic analyses evidently confirmed micro-colony formation, biofilm thickness and surface coverage were reduced upon DD treatment. In addition, based on the results of in vitro assays, it was noted that DD impaired the synthesis of surface hydrophobicity, slime, hyaluronic acid, hemolysin and protease production. Interestingly, DD increased the autoaggregation of S. pyogenes hence, facilitated enhanced recognition of clumped bacterial cells for innate immune clearance. The results were further validated by the reduced survival of DD treated S. pyogenes in healthy human blood. Consequently, based on the qPCR analysis DD altered the expression of core regulons srv, ropB, mga and genes associated with biofilm formation and virulence such as speB, dltA, srtB, sagA and slo. Hence, the overall results of the present study for the first time revealed the antibiofilm and antivirulence property of DD against clinically important pathogen S. pyogenes and further clinical investigations are required to assess the therapeutic use of DD.

Keywords: Biofilm; Dodecanolide; Group A Streptococcus; Streptococcus pyogenes; Virulence.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Biofilms / drug effects*
  • Colony-Forming Units Assay
  • Gene Expression Regulation, Bacterial
  • Humans
  • Streptococcus pyogenes / drug effects*
  • Streptococcus pyogenes / genetics
  • Streptococcus pyogenes / pathogenicity
  • Virulence / drug effects
  • Virulence / genetics

Substances

  • Anti-Bacterial Agents