Suppression of virulence factors of uropathogenic Escherichia coli by Trans-resveratrol and design of nanoemulgel

BMC Microbiol. 2024 Oct 17;24(1):412. doi: 10.1186/s12866-024-03538-4.

Abstract

Background: Development of multidrug resistance in Uropathogenic Escherichia coli (UPEC) makes treatment of Urinary Tract Infections (UTIs) a major challenge. This study was conducted to investigate the effect of trans-resveratrol (t-RSV) at a subinhibitory concentration (sub-MIC-t-RSV) on phenotypic and genotypic expression of virulence factors of clinical isolates of UPEC and develop a nanoformulation of t-RSV. Fifty-five clinical UPEC strains were investigated for the presence of virulence factors by phenotypic methods and PCR detection of virulence genes. The effect of sub-MIC-t-RSV was studied on the phenotypic and genotypic expression of virulence factors. t-RSV-loaded nanoemulgel formulation was prepared and characterized.

Results: Out of the 55 tested isolates, 50.9% were biofilm producers, 23.6% showed both mannose-sensitive and mannose-resistant hemagglutination, 21.8% were serum-resistant, 18.2% were hemolysin producers, while 36.4% showed cytotoxic effect on HEp-2 cells. A total of 25.5% of the isolates harbor one or more of hly-A, cnf-1 and papC genes, while 54.5% were positive for one or more of fimH, iss and BssS genes. A concentration of 100 µg/mL of t-RSV effectively downregulates the phenotypic and genotypic expression of the virulence factors in positive isolates. A stable t-RSV-nanaoemulgel with droplet size of 180.3 nm and Zetapotential of -46.9 mV was obtained.

Conclusion: The study proves the effective role of t-RSV as an antivirulence agent against clinical UPEC isolates in vitro and develops a stable t-RSV-nanoemulgel formulation to be assessed in vivo. The promising antibacterial and antivirulence properties of t-RSV place this natural compound to be a better alternative in the treatment of persistent UTIs.

Keywords: Gene expression; Nanoemulgel; Trans-resveratrol; UPEC; Virulence factors.

MeSH terms

  • Anti-Bacterial Agents* / pharmacology
  • Biofilms* / drug effects
  • Biofilms* / growth & development
  • Escherichia coli Infections* / drug therapy
  • Escherichia coli Infections* / microbiology
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Gels / chemistry
  • Humans
  • Microbial Sensitivity Tests*
  • Nanoparticles / chemistry
  • Resveratrol* / chemistry
  • Resveratrol* / pharmacology
  • Stilbenes / chemistry
  • Stilbenes / pharmacology
  • Urinary Tract Infections / drug therapy
  • Urinary Tract Infections / microbiology
  • Uropathogenic Escherichia coli* / drug effects
  • Uropathogenic Escherichia coli* / genetics
  • Uropathogenic Escherichia coli* / pathogenicity
  • Virulence Factors* / genetics

Substances

  • Virulence Factors
  • Resveratrol
  • Anti-Bacterial Agents
  • Stilbenes
  • Escherichia coli Proteins
  • Gels