title: New insights into the translocation route of enrofloxacin and its metalloantibiotics.
abstract: Probing drug/lipid interactions at the molecular level represents an important challenge in pharmaceutical research, drug discovery and membrane biophysics. Previous studies showed that enrofloxacin metalloantibiotic has potential as an antimicrobial agent candidate, since it exhibits antimicrobial effect comparable to that of free enrofloxacin but a different translocation route. These differences in uptake mechanism can be paramount in counteracting bacterial resistance. In view of lipids role in bacterial drug uptake, the interaction of these compounds with different Escherichia coli model membranes were studied by fluorescence spectroscopy. Partition coefficients determined showed that lipid/antibiotic interactions were sensitive to liposomes composition and that the metalloantibiotic had a higher partition than free enrofloxacin. These results corroborate the different mechanism of entry proposed and can be rationalized on the basis that an electrostatic interaction between the metalloantibiotic positively charged species, present at physiological pH, and the lipids negatively charged head groups clearly promotes the lipid/antimicrobial association.
authors.affiliation: Requimte, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre, 4169-007 Porto, Portugal. carla.alex.gomes.ribeiro@gmail.com
authors.forename: C
authors.initials: C
authors.lastname: Ribeiro
authors.forename: S C
authors.initials: SC
authors.lastname: Lopes
authors.forename: P
authors.initials: P
authors.lastname: Gameiro
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects*; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D056831:Coordination Complexes / Q000378:metabolism / Q000494:pharmacology*; D003300:Copper / Q000378:metabolism; D024881:Drug Resistance, Bacterial; D000077422:Enrofloxacin; D004926:Escherichia coli / Q000737:chemistry*; D024841:Fluoroquinolones / Q000378:metabolism / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism*; D010618:Phenanthrolines / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D055672:Static Electricity
chemical_list: D000900:Anti-Bacterial Agents; D056831:Coordination Complexes; D024841:Fluoroquinolones; D008051:Lipid Bilayers; D008081:Liposomes; D010618:Phenanthrolines; D010743:Phospholipids; D000077422:Enrofloxacin; D003300:Copper