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

• Type: Article in International Scientific Journal
• Date: 2013

Authors

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

Journal

Title: Journal of Physical Chemistry B

Vol. 117

Pages: 6187-6193

ISSN: 1520-6106

Publisher: American Chemical Society

Indexing

ISI Web of Knowledge - 14 Citations

Scopus - 16 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7