Recognition of Membrane Sterols by Polyene Antifungals Amphotericin B and Natamycin, A 13C MAS NMR Study

Abstract

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.

Aspergillus fumigatus and Aspergillosis in 2019

“…To date, no resistance problems associated with echinocandins and amphotericin B have been identified in clinics. However, echinocandin-resistant mutants can be induced easily in vitro (630,631), and hot spots for point mutations inducing the resistance to amphotericin were identified in A. fumigatus after use of natamycin (632)(633)(634) and are starting to be seen in laboratories (635,636). However, resistance to AMB is only anecdotal.…”

Investigating selective media for optimal isolation of Brucella spp. in South Africa

“…In this study, the inhibition of fungal growth by natamycin was shown by the performance of FM, which inhibited the growth of most fungal contaminants throughout the study in spite of the medium inhibiting the growth of B. ovis as well. Previous studies have shown that amphotericin B and natamycin have different modes of action even though they both belong to the macrolide polyene class of antibiotics (Ciesielski et al 2016;Lalitha et al 2010). Furthermore, te Welscher et al ( 2008) also reported that natamycin, filipin and nystatin have different mode of action as well.…”

Influence of the salt concentration on action mechanisms of natamycin against microorganisms of importance in food manufacture

“…These interactions, added to the action of natamycin on C. albicans and E. coli, lead to a reduction in the final count of these microorganisms. Natamycin has an antimycotic action because of its preference for ergosterol, a sterol present especially in the cell membrane of fungi and little found in bacteria (Ciesielski et al, 2016).…”