Complex formation between primycin and ergosterol: entropy–driven initiation of modification of the fungal plasma membrane structure

Abstract

The interaction of the antibiotic primycin with the main fungal sterol, ergosterol, was investigated in vitro in order to monitor the effect of primycin on the fungal plasma membrane at the molecular level. The thermodynamic parameters of complex formation were determined by measuring Rayleigh scattering as a signal sensitive to particle size. The Benesi-Hildebrand method validated the 1 : 1 stoichiometry of the primycin-ergosterol complexes. A very low enthalpy change (ΔH=-1.14 kJ mol(-1)) was measured during the complex formation, which itself cannot be responsible for the molecular association. However, the entropy production (ΔS=29.78 J mol K(-1)) observed during the complex formation can describe the molecular interaction. This effect is probably due to the partial destruction of the solvation shell of the interacting species before the interlinking of the molecules. The results highlight the importance of ergosterol as concerns the mode of effect of primycin in the treatment of fungal infections. As the entropy has a determinant role in the ergosterol-primycin interaction, this interaction exhibits a very high temperature dependence, with the important consequence that the effect exerted by primycin on the cell membranes increases with rising temperature, and the effect is therefore pronounced in fevered bodies.

In Vitro Anti-Candida Activity and Action Mode of Benzoxazole Derivatives

“…Benzoxazoles inhibited these important processes by binding to ergosterol; thus, sterols could not perform their functional effects [ 43 ]. In line with Escalante et al [ 44 ] and Virág et al [ 45 ], during the interaction of 8d and 8f with ergosterol, we considered the possible formation of complexes between the carboxyl group of ergosterol and the OH groups of benzoxazoles (dative bounds) as well as hydrogen bounds. The activity of 5a , 5j , 8i and 8c ( Figure S1 ) remained unchanged in the presence of exogenous ergosterol, suggesting that they did not interact with the membrane ergosterol.…”

Cytotoxic Action of Artemisinin and Scopoletin on Planktonic Forms and on Biofilms of Candida Species

“…This can also facilitate the permeability of the cell membrane and incorporation of propidium iodide through the compromised membranes into the cells. Further characterization of the effects of Ar and Sc on the levels of superoxide dismutase and catalase at increased ROS level must be assessed [26,28]. Moreover, Ar also plays an important role in the electron transport chain by overexpressing nuclear distribution protein nude homolog 1 (NDE 1 ) that is responsible for encoding mitochondrial NADH dehydrogenases causing sensitivity to Ar followed by membrane disruption resulting in mitochondrial dysfunction by the higher free radical generation when compared to Sc [29,30].…”

The genus Micromonospora as a model microorganism for bioactive natural product discovery

“…38 In 2003, their biosynthetic gene cluster was completely determined in M. griseorubida suggesting that some genes in the cluster might have been horizontally transferred from Streptomyces spp. 39 The large non-polyene macrolide perimycin (45) was rst isolated from Streptomyces primycini and showed potent antibiotic activity towards Gram-positive bacteria. 40 Later, it was obtained in a higher quantity from M. galareinsis.…”

“…44 Its complex formation with the fungal cell membrane ergosterol is considered the primary mode of action responsible for its antifungal properties. 45 All Micromonospora-derived antimicrobial macrolides are depicted in The rst anticancer macrolide recovered from Micromonospora was in 1993, when the 60-membered polyene macrolides quinolidomicins A1, A2 and B1 (46)(47)(48) were isolated and characterized from a soil-derived M. chalcea. 46 Both quinolidomicins A1 and B1 (46,48) demonstrated signicantly potent in vitro antiproliferative activity (IC 50 25-327 ng mL À1 ) toward an array of human cancer cell lines including multidrug-resistant cells.…”