Polyphenolic Secondary Metabolites Synergize the Activity of Commercial Antibiotics against Clinical Isolates of β-Lactamase-producing Klebsiella pneumoniae

Phytother Res. 2016 Feb;30(2):272-82. doi: 10.1002/ptr.5527. Epub 2015 Dec 14.

Abstract

Emergence of worldwide antimicrobial resistance prompted us to study the resistance modifying potential of plant-derived dietary polyphenols, mainly caffeic acid, ellagic acid, epigallocatechin-3-gallate (EGCG) and quercetin. These compounds were studied in logical combination with clinically significant antibiotics (ciprofloxacin/gentamicin/tetracycline) against Klebsiella pneumoniae, after conducting phenotypic screening of a large number of clinical isolates and selecting the relevant strains possessing extended-spectrum β-lactamase (ESBL) and K. pneumoniae carbapenemase (KPC)-type carbapenemase enzymes only. The study demonstrated that EGCG and caffeic acid could synergize the activity of tested antibiotics within a major population of β-lactamase-producing K. pneumoniae. In spectrofluorimetric assay, ~17-fold greater ciprofloxacin accumulation was observed within K. pneumoniae cells pre-treated with EGCG in comparison with the untreated control, indicating its ability to synergize ciprofloxacin to restrain active drug-efflux. Further, electron micrograph of ESBL-producing K. pneumoniae clearly demonstrated the prospective efficacy of EGCG towards biofilm degradation.

Keywords: KPC-type carbapenemase; Klebsiella pneumoniae; antimicrobial synergy; caffeic acid; epigallocatechin-3-gallate; extended-spectrum β-lactamase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / metabolism
  • Caffeic Acids / pharmacology
  • Catechin / analogs & derivatives
  • Catechin / pharmacology
  • Ciprofloxacin / pharmacology
  • Drug Synergism
  • Ellagic Acid / pharmacology
  • Gentamicins / pharmacology
  • Klebsiella pneumoniae / drug effects*
  • Klebsiella pneumoniae / enzymology
  • Microbial Sensitivity Tests
  • Phytochemicals / pharmacology*
  • Polyphenols / pharmacology*
  • Quercetin / pharmacology
  • Reserpine / pharmacology
  • Tetracycline / pharmacology
  • beta-Lactamases / metabolism

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Caffeic Acids
  • Gentamicins
  • Phytochemicals
  • Polyphenols
  • Ellagic Acid
  • Ciprofloxacin
  • Reserpine
  • Catechin
  • Quercetin
  • epigallocatechin gallate
  • beta-Lactamases
  • carbapenemase
  • Tetracycline
  • caffeic acid