title: Polyphenolic Secondary Metabolites Synergize the Activity of Commercial Antibiotics against Clinical Isolates of β-Lactamase-producing Klebsiella pneumoniae.
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.
authors.affiliation: Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700032, India.|Department of Microbiology, Ashok Laboratory Clinical Testing Centre Private Limited, Kolkata, 700068, India.
authors.forename: Diganta
authors.initials: D
authors.lastname: Dey
authors.affiliation: Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700032, India.
authors.forename: Subhalakshmi
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Department of Microbiology, Ashok Laboratory Clinical Testing Centre Private Limited, Kolkata, 700068, India.
authors.forename: Ratnamala
authors.initials: R
authors.lastname: Ray
authors.affiliation: Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700032, India.
authors.forename: Banasri
authors.initials: B
authors.lastname: Hazra
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000378:metabolism; D002109:Caffeic Acids / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D002939:Ciprofloxacin / Q000494:pharmacology; D004357:Drug Synergism; D004610:Ellagic Acid / Q000494:pharmacology; D005839:Gentamicins / Q000494:pharmacology; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000201:enzymology; D008826:Microbial Sensitivity Tests; D064209:Phytochemicals / Q000494:pharmacology*; D059808:Polyphenols / Q000494:pharmacology*; D011794:Quercetin / Q000494:pharmacology; D012110:Reserpine / Q000494:pharmacology; D013752:Tetracycline / Q000494:pharmacology; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002109:Caffeic Acids; D005839:Gentamicins; D064209:Phytochemicals; D059808:Polyphenols; D004610:Ellagic Acid; D002939:Ciprofloxacin; D012110:Reserpine; D002392:Catechin; D011794:Quercetin; C045651:epigallocatechin gallate; D001618:beta-Lactamases; C063912:carbapenemase; D013752:Tetracycline; C040048:caffeic acid
keywords: KPC-type carbapenemase; Klebsiella pneumoniae; antimicrobial synergy; caffeic acid; epigallocatechin-3-gallate; extended-spectrum β-lactamase