title: Mechanisms of ceftazidime and ciprofloxacin transport through porins in multidrug-resistance developed by extended-spectrum beta-lactamase E.coli strains.
abstract: Resistance towards antibiotics stands out today as a major issue in the clinical act of treatment of bacterial-generated infections. This process was characterized in proteoliposomes reconstituted from an E.coli strain isolated from invasive infections (blood culture) occurred in patients with a cardio-vascular device admitted for surgery. Fluorescence spectroscopy and patch-clamp technique have been used. Two types of antibiotics have been targeted: ceftazidime and ciprofloxacin. Antibiotics addition in proteoliposomes suspension undergoes a quenching in tryptophan residues from outer membrane porins structure, probably due to the formation of a transient non-fluorescent porin-antibiotic complex. Patch-clamp recordings revealed strong ion current blockages for both antibiotics, reflecting antibiotic-channel interactions but with varying strength of interaction. The present study puts forward the mechanism of multidrug-resistance in extended-spectrum beta-lactamase E.coli strains, as being caused by alterations of the antibiotics transport across the porins of the outer bacterial membrane.
authors.affiliation: Department of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, Splaiul Independentei, 91-95, Bucharest 050095, Romania. beatrice_macri@yahoo.com
authors.forename: Beatrice Mihaela
authors.initials: BM
authors.lastname: Radu
authors.forename: Mihaela
authors.initials: M
authors.lastname: Bacalum
authors.forename: Adela
authors.initials: A
authors.lastname: Marin
authors.forename: Carmen-Mariana
authors.initials: CM
authors.lastname: Chifiriuc
authors.forename: Veronica
authors.initials: V
authors.lastname: Lazar
authors.forename: Mihai
authors.initials: M
authors.lastname: Radu
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002442:Ceftazidime / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology; D005453:Fluorescence; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D008826:Microbial Sensitivity Tests; D018272:Porins / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D018272:Porins; D065093:beta-Lactamase Inhibitors; D002939:Ciprofloxacin; D002442:Ceftazidime; D001618:beta-Lactamases