Comparing the interaction of the antibiotic levofloxacin with zwitterionic and anionic membranes: Calorimetry, fluorescence, and spin label studies.

Autor: Vignoli Muniz GS; Instituto de Física, Universidade de São Paulo, São Paulo, SP CEP 05508-090, Brazil. Electronic address: gvignoli@if.usp.br., Souza MC; Instituto de Física, Universidade de São Paulo, São Paulo, SP CEP 05508-090, Brazil., Duarte EL; Instituto de Física, Universidade de São Paulo, São Paulo, SP CEP 05508-090, Brazil., Lamy MT; Instituto de Física, Universidade de São Paulo, São Paulo, SP CEP 05508-090, Brazil. Electronic address: mtlamy@usp.br.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Biomembranes [Biochim Biophys Acta Biomembr] 2021 Jul 01; Vol. 1863 (7), pp. 183622. Date of Electronic Publication: 2021 Apr 15.
DOI: 10.1016/j.bbamem.2021.183622
Abstrakt: The present work compares the interaction of the antibiotic levofloxacin (LVX) with zwitterionic and anionic liposomes composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DPPG), respectively. By using differential scanning calorimetry (DSC), and with spin labels incorporated into liposomes at two different depths of the bilayers, we investigated the changes induced on the membrane by increasing concentrations of LVX. Further information was obtained using intrinsic LVX fluorescence. Under the conditions used here, all techniques evinced that LVX has little affinity for DPPC zwitterionic membrane. Opposite to that, LVX exhibits a considerable affinity for anionic bilayers, with membrane partition constants K p  = (3.3 ± 0.5) × 10 2 and (4.5 ± 0.3) × 10 2 , for gel and fluid DPPG membranes, respectively. On binding to DPPG, LVX seems to give rise to the coexistence of LVX -rich and -poor domains on DPPG membranes, as detected by DSC. At the highest LVX concentration used (20 mol%), DSC trace shows an increase in the cooperativity of DPPG gel-fluid transition, also detected by spin labels as an increase in the bilayer packing. Moreover, LVX does not induce pore formation in either DPPG or POPG vesicles. Considering the possible relevance of LVX-membrane interaction for the biological and toxicological action of the antibiotic, the findings discussed here certainly contribute to a better understanding of its action, and the planning of new drugs.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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