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1.
Biochim Biophys Acta Biomembr ; 1863(1): 183448, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-32828850

RESUMO

Numerous antibiotics are known to target intracellular pathways, such as protein translation or DNA replication. Membrane transporters typically regulate drug uptake; however, little is known about direct interactions between these antibiotics and the cell membranes. Here, we studied the interactions between different aminoglycosides (kanamycin, gentamicin, streptomycin, neomycin), macrolides (azithromycin, clarithromycin, erythromycin), and fluoroquinolones (ciprofloxacin, levofloxacin) with bacterial membrane mimics to determine drug partitioning and potential drug-induced membrane disruption. The antibiotics' exact location in the bilayers and their effect on membrane thickness and fluidity were determined from high-resolution X-ray diffraction. While the antibiotics did not change membrane thickness at low (1:100 drug/lipid) or high (1:10 drug/lipid) concentrations, they were found to increase membrane disorder in a dose-dependent manner. However, no membrane damage, such as membrane disruption or pore formation, was observed for any of the antibiotics. To note, all antibiotics partitioned into the lipid head groups, while macrolides and fluoroquinolones also partitioned into the bilayer core. The results suggest that the bacterial membrane is relatively inert in the direct mechanisms of actions of these antibiotics.


Assuntos
Antibacterianos/química , Bactérias/química , Membrana Celular/química , Bicamadas Lipídicas/química , Difração de Raios X
2.
Langmuir ; 36(40): 11899-11907, 2020 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-32903014

RESUMO

The safe storage of blood is of fundamental importance to health care systems all over the world. Currently, plastic bags are used for the collection and storage of donated blood and are typically made of poly(vinyl chloride) (PVC) plasticized with di-2-ethylhexyl phthalate (DEHP). DEHP is known to migrate into packed red blood cells (RBC) and has been found to extend their shelf life. It has been speculated that DEHP incorporates itself into the RBC membrane and alters membrane properties, thereby reducing susceptibility to hemolysis and morphological deterioration. Here, we used high-resolution X-ray diffraction and molecular dynamics (MD) simulations to study the interaction between DEHP and model POPC lipid membranes at high (9 mol %) and low (1 mol %) concentrations of DEHP. At both concentrations, DEHP was found to spontaneously partition into the bilayer. At high concentrations, DEHP molecules were found to aggregate in the aqueous phase before inserting as clusters into the membrane. The presence of DEHP in the bilayers resulted in subtle, yet statistically significant, alterations in several membrane properties in both the X-ray diffraction experiments and MD simulations. DEHP led to (1) an increase of membrane width and (2) an increase in the area per lipid. It was also found to (3) increase the deuterium order parameter, however, (4) decrease membrane orientation, indicating the formation of thicker, stiffer membranes with increased local curvature. The observed effects of DEHP on lipid bilayers may help to better understand its effect on RBC membranes in increasing the longevity of stored blood by improving membrane stability.


Assuntos
Dietilexilftalato , Plastificantes , Preservação de Sangue , Dietilexilftalato/toxicidade , Eritrócitos , Lipídeos , Ácidos Ftálicos , Plastificantes/toxicidade , Cloreto de Polivinila
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