Recognition of membrane sterols by polyene antifungals amphotericin B and natamycin, a 13C MAS NMR Study
The molecular action of polyene macrolides with antifungal activity, amphotericin B and natamycin, involves recognition of sterols in membranes. Physicochemical and functional studies have contributed details to understanding the interactions between amphotericin B and ergosterol and, to a lesser ex...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Published: |
Frontiers Media
2016
|
| Subjects: | |
| Online Access: | https://eprints.nottingham.ac.uk/34649/ |
| _version_ | 1848794902670868480 |
|---|---|
| author | Ciesielski, Filip Griffin, David C. Loraine, Jessica Rittig, Michael Delves-Broughton, Joss Bonev, Boyan B. |
| author_facet | Ciesielski, Filip Griffin, David C. Loraine, Jessica Rittig, Michael Delves-Broughton, Joss Bonev, Boyan B. |
| author_sort | Ciesielski, Filip |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | The molecular action of polyene macrolides with antifungal activity, amphotericin B and natamycin, involves recognition of sterols in membranes. Physicochemical and functional studies have contributed details to understanding the interactions between amphotericin B and ergosterol and, to a lesser extent, with cholesterol. Fewer molecular details are available on interactions between natamycin with sterols. We use solid state 13C MAS NMR to characterize the impact of amphotericin B and natamycin on mixed lipid membranes of DOPC/cholesterol or DOPC/ergosterol. In cholesterol-containing membranes, amphotericin B addition resulted in marked increase in both DOPC and cholesterol 13C MAS NMR linewidth, reflecting membrane insertion and cooperative perturbation of the bilayer. By contrast, natamycin affects little either DOPC or cholesterol linewidth but attenuates cholesterol resonance intensity preferentially for sterol core with lesser impact on the chain. Ergosterol resonances, attenuated by amphotericin B, reveal specific interactions in the sterol core and chain base. Natamycin addition selectively augmented ergosterol resonances from sterol core ring one and, at the same time, from the end of the chain. This puts forward an interaction model similar to the head-to-tail model for amphotericin B/ergosterol pairing but with docking on opposite sterol faces. Low toxicity of natamycin is attributed to selective, non-cooperative sterol engagement compared to cooperative membrane perturbation by amphotericin B. |
| first_indexed | 2025-11-14T19:23:34Z |
| format | Article |
| id | nottingham-34649 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:23:34Z |
| publishDate | 2016 |
| publisher | Frontiers Media |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-346492020-05-04T17:56:03Z https://eprints.nottingham.ac.uk/34649/ Recognition of membrane sterols by polyene antifungals amphotericin B and natamycin, a 13C MAS NMR Study Ciesielski, Filip Griffin, David C. Loraine, Jessica Rittig, Michael Delves-Broughton, Joss Bonev, Boyan B. The molecular action of polyene macrolides with antifungal activity, amphotericin B and natamycin, involves recognition of sterols in membranes. Physicochemical and functional studies have contributed details to understanding the interactions between amphotericin B and ergosterol and, to a lesser extent, with cholesterol. Fewer molecular details are available on interactions between natamycin with sterols. We use solid state 13C MAS NMR to characterize the impact of amphotericin B and natamycin on mixed lipid membranes of DOPC/cholesterol or DOPC/ergosterol. In cholesterol-containing membranes, amphotericin B addition resulted in marked increase in both DOPC and cholesterol 13C MAS NMR linewidth, reflecting membrane insertion and cooperative perturbation of the bilayer. By contrast, natamycin affects little either DOPC or cholesterol linewidth but attenuates cholesterol resonance intensity preferentially for sterol core with lesser impact on the chain. Ergosterol resonances, attenuated by amphotericin B, reveal specific interactions in the sterol core and chain base. Natamycin addition selectively augmented ergosterol resonances from sterol core ring one and, at the same time, from the end of the chain. This puts forward an interaction model similar to the head-to-tail model for amphotericin B/ergosterol pairing but with docking on opposite sterol faces. Low toxicity of natamycin is attributed to selective, non-cooperative sterol engagement compared to cooperative membrane perturbation by amphotericin B. Frontiers Media 2016-06-17 Article PeerReviewed Ciesielski, Filip, Griffin, David C., Loraine, Jessica, Rittig, Michael, Delves-Broughton, Joss and Bonev, Boyan B. (2016) Recognition of membrane sterols by polyene antifungals amphotericin B and natamycin, a 13C MAS NMR Study. Frontiers in Cell and Developmental Biology, 4 . p. 57. ISSN 2296-634X Antimicrobials antifungals membranes cholesterol ergosterol 13C solid state MAS NMR receptor recognition http://journal.frontiersin.org/article/10.3389/fcell.2016.00057/full doi:10.3389/fcell.2016.00057 doi:10.3389/fcell.2016.00057 |
| spellingShingle | Antimicrobials antifungals membranes cholesterol ergosterol 13C solid state MAS NMR receptor recognition Ciesielski, Filip Griffin, David C. Loraine, Jessica Rittig, Michael Delves-Broughton, Joss Bonev, Boyan B. Recognition of membrane sterols by polyene antifungals amphotericin B and natamycin, a 13C MAS NMR Study |
| title | Recognition of membrane sterols by polyene antifungals amphotericin B and natamycin, a 13C MAS NMR Study |
| title_full | Recognition of membrane sterols by polyene antifungals amphotericin B and natamycin, a 13C MAS NMR Study |
| title_fullStr | Recognition of membrane sterols by polyene antifungals amphotericin B and natamycin, a 13C MAS NMR Study |
| title_full_unstemmed | Recognition of membrane sterols by polyene antifungals amphotericin B and natamycin, a 13C MAS NMR Study |
| title_short | Recognition of membrane sterols by polyene antifungals amphotericin B and natamycin, a 13C MAS NMR Study |
| title_sort | recognition of membrane sterols by polyene antifungals amphotericin b and natamycin, a 13c mas nmr study |
| topic | Antimicrobials antifungals membranes cholesterol ergosterol 13C solid state MAS NMR receptor recognition |
| url | https://eprints.nottingham.ac.uk/34649/ https://eprints.nottingham.ac.uk/34649/ https://eprints.nottingham.ac.uk/34649/ |