The Influence of Rifabutin on Human and Bacterial Membrane Models: Implications for Its Mechanism of Action

• Tipo: Artigo em Revista Científica Internacional
• Data: 2013

Autores

Marina Pinheiro (Autor) Outra; Claudia Nunes (Autor) Outra; Joao M Caio (Autor) Outra; Cristina Moiteiro (Autor) Outra; Marlene Lucio (Autor) FFUP; Gerald Brezesinski (Autor) Outra; Salette Reis (Autor) FFUP

Revista

Título: Journal of Physical Chemistry B

Vol. 117

Páginas: 6187-6193

ISSN: 1520-6106

Editora: American Chemical Society

Indexação

ISI Web of Knowledge - 14 Citações

Scopus - 16 Citações

Classificação Científica

FOS: Ciências exactas e naturais > Química

Outras Informações

ID Authenticus: P-005-0NS

DOI: 10.1021/jp403073v

Abstract (EN): This work focuses on the interaction of the antibiotic Rifabutin (RFB) with phospholipid membrane models using small-and wide-angle X-ray scattering (SAXS and WAXS) to assess drug membrane interactions. The effect of different concentrations of RFB on human and bacterial cell membrane models was studied using multilamellar vesicles (MLVs) at the physiological pH (7.4). In this context, MLVs of 1,2-dimyristoyl-rac-glycero-3-phosphocholine (DMPC) were chosen to mimic the human cell membrane. To mimic the bacterial cell membrane, 1,2-dimyristoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DMPG) and a mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) and 1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DPPG) (8:2 molar ratio) were used. The results support a perturbation of the lipid bilayers caused by RFB, especially in the bacterial membrane model, inducing phase separation that might compromise the integrity of the bacterial membrane. Therefore, the different effects of this antibiotic depending on the concentration, the charge of the phospholipid headgroup, and the membrane organization may be related with the RFB antibiotic activity and the side effects, and should be accounted for during the anti-tuberculosis (anti-TB) drug design.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 7