Literature DB >> 19929013

On the possibility of the amphotericin B-sterol complex formation in cholesterol- and ergosterol-containing lipid bilayers: a molecular dynamics study.

Anna Neumann1, Jacek Czub, Maciej Baginski.   

Abstract

Amphotericin B (AmB) is a well-known membrane-active antibiotic that has been used to treat systemic fungal infections for more than 45 years. Therapeutic application of AmB is based on the fact that it is more active against ergosterol-containing membranes of fungal cells than against mammalian membranes with cholesterol. In this paper, we examine the hypothesis according to which the selectivity of the AmB's membrane action originates from its different ability to form the binary complexes with the relevant sterols. To this end, molecular dynamics simulations were performed for systems containing the preformed models of AmB/sterol complexes embedded in lipid bilayers containing either cholesterol or ergosterol. The initial structures of the studied binary associates were selected on the basis of a systematic scan of all possible mutual positions and orientations of the two molecules. The results obtained demonstrate that in general the complexes with ergosterol are more stable on the 100 ns time scale. Furthermore, on the basis of motional correlation analysis, taking into account the effects of lipid environment, we propose that, within the sterol-enriched liquid-ordered membrane phases, AmB molecules exhibit a greater tendency to bind ergosterol than cholesterol. The analysis of the interactions suggests that this affinity difference is of enthalpic origin and may arise from the considerable difference in the energy of the van der Waals interactions between AmB and the two types of sterols. Thus, our current results: (i) support the hypothesis that binary AmB/sterol complexes form within a lipid membrane and (ii) suggest that the higher toxicity may at least partly be attributed to the higher affinity of AmB for ergosterol than for cholesterol within a lipid membrane environment.

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Year:  2009        PMID: 19929013     DOI: 10.1021/jp905133f

Source DB:  PubMed          Journal:  J Phys Chem B        ISSN: 1520-5207            Impact factor:   2.991


  15 in total

1.  Synthesis-enabled functional group deletions reveal key underpinnings of amphotericin B ion channel and antifungal activities.

Authors:  Daniel S Palacios; Ian Dailey; David M Siebert; Brandon C Wilcock; Martin D Burke
Journal:  Proc Natl Acad Sci U S A       Date:  2011-02-28       Impact factor: 11.205

2.  C2'-OH of amphotericin B plays an important role in binding the primary sterol of human cells but not yeast cells.

Authors:  Brandon C Wilcock; Matthew M Endo; Brice E Uno; Martin D Burke
Journal:  J Am Chem Soc       Date:  2013-06-03       Impact factor: 15.419

3.  Towards New Insights in the Sterol/Amphotericin Nanochannels Formation: A Molecular Dynamic Simulation Study.

Authors:  Khaoula Boukari; Sébastien Balme; Jean-Marc Janot; Fabien Picaud
Journal:  J Membr Biol       Date:  2015-12-23       Impact factor: 1.843

4.  The effect of sterols on amphotericin B self-aggregation in a lipid bilayer as revealed by free energy simulations.

Authors:  Anna Neumann; Maciej Baginski; Szymon Winczewski; Jacek Czub
Journal:  Biophys J       Date:  2013-04-02       Impact factor: 4.033

Review 5.  Lipid Systems for the Delivery of Amphotericin B in Antifungal Therapy.

Authors:  Célia Faustino; Lídia Pinheiro
Journal:  Pharmaceutics       Date:  2020-01-01       Impact factor: 6.321

6.  Probing amphotericin B single channel activity by membrane dipole modifiers.

Authors:  Olga S Ostroumova; Svetlana S Efimova; Ludmila V Schagina
Journal:  PLoS One       Date:  2012-01-19       Impact factor: 3.240

7.  Investigation of channel-forming activity of polyene macrolide antibiotics in planar lipid bilayers in the presence of dipole modifiers.

Authors:  S S Efimova; L V Schagina; O S Ostroumova
Journal:  Acta Naturae       Date:  2014-10       Impact factor: 1.845

8.  Electronic tuning of site-selectivity.

Authors:  Brandon C Wilcock; Brice E Uno; Gretchen L Bromann; Matthew J Clark; Thomas M Anderson; Martin D Burke
Journal:  Nat Chem       Date:  2012-12       Impact factor: 24.427

Review 9.  Recent progress in the study of the interactions of amphotericin B with cholesterol and ergosterol in lipid environments.

Authors:  Daniel Michał Kamiński
Journal:  Eur Biophys J       Date:  2014-08-31       Impact factor: 1.733

10.  Unveiling the Synergistic Interaction Between Liposomal Amphotericin B and Colistin.

Authors:  Rita Teixeira-Santos; Elisabete Ricardo; Ricardo J Branco; Maria M Azevedo; Acácio G Rodrigues; Cidália Pina-Vaz
Journal:  Front Microbiol       Date:  2016-09-13       Impact factor: 5.640

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