Mechanisms of ceftazidime and ciprofloxacin transport through porins in multidrug-resistance developed by extended-spectrum beta-lactamase E.coli strains

J Fluoresc. 2011 Jul;21(4):1421-9. doi: 10.1007/s10895-010-0826-7. Epub 2011 Jan 14.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology*
  • Biological Transport / drug effects
  • Ceftazidime / chemistry
  • Ceftazidime / metabolism
  • Ceftazidime / pharmacology*
  • Ciprofloxacin / chemistry
  • Ciprofloxacin / metabolism
  • Ciprofloxacin / pharmacology*
  • Drug Resistance, Multiple, Bacterial / drug effects*
  • Escherichia coli / drug effects*
  • Escherichia coli / enzymology
  • Fluorescence
  • Fluorescence Resonance Energy Transfer
  • Humans
  • Microbial Sensitivity Tests
  • Porins / chemistry
  • Porins / metabolism*
  • Structure-Activity Relationship
  • beta-Lactamase Inhibitors*
  • beta-Lactamases / metabolism

Substances

  • Anti-Bacterial Agents
  • Porins
  • beta-Lactamase Inhibitors
  • Ciprofloxacin
  • Ceftazidime
  • beta-Lactamases