PLoS One 2016;11(9):e0162171. Epub 2016 Sep 28.
Instituto de Ciencias Físicas, Universidad Nacional Autónoma de México, Apartado Postal 48-3, 62251, Cuernavaca, Morelos, México.
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J Gen Physiol 1970 Mar;55(3):375-400
Amphotericin B modifies the permeability properties of thin lipid membranes formed from solutions containing sheep red cell phospholipids and cholesterol. At 10(-6)M amphotericin B, the DC membrane resistance fell from approximately 10(8) to approximately 10(2) ohm-cm(2), and the membranes became Cl(-)-, rather than Na(+)-selective; the permeability coefficients for hydrophilic nonelectrolytes increased in inverse relationship to solute size, and the rate of water flow during osmosis increased 30-fold. These changes may be rationalized by assuming that the interaction of amphotericin B with membrane-bound sterol resulted in the formation of aqueous pores. Read More
J Gen Physiol 1970 Jul;56(1):100-24
Characteristics of nystatin and amphotericin B action on thin (<100 A) lipid membranes are: (a) micromolar amounts increase membrane conductance from 10(-8) to over 10(-2) Omega(-1) cm(-2); (b) such membranes are (non-ideally) anion selective and discriminate among anions on the basis of size; (c) membrane sterol is required for action; (d) antibiotic presence on both sides of membrane strongly favors action; (e) conductance is proportional to a large power of antibiotic concentration; (f) conductance decreases approximately 10(4) times for a 10 degrees C temperature rise; (g) kinetics of antibiotic action are also very temperature sensitive; (h) ion selectivity is pH independent between 3 and 10, but (i) activity is reversibly lost at high pH; (j) methyl ester derivatives are fully active; N-acetyl and N-succinyl derivatives are inactive; (k) current-voltage characteristic is nonlinear when membrane separates nonidentical salt solutions. These characteristics are contrasted with those of valinomycin. Observations (a)-(g) suggest that aggregates of polyene and sterol from opposite sides of the membrane interact to create aqueous pores; these pores are not static, but break up (melt) and reform continuously. Read More
J Colloid Interface Sci 2005 Jul;287(2):476-84
Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Kraków, Poland.
N-(1-piperidinepropionyl)amphotericin B methyl ester (in short, PAME), a low-toxicity amphotericin B derivative, has been investigated in Langmuir monolayers at the air/water interface alone and in mixtures with cellular membrane sterols (a mammalian sterol, cholesterol, and a fungal sterol, ergosterol) and a model phospholipid (DPPC). The analysis of the strength of interaction between PAME and both sterols as well as DPPC was based, on surface pressure measurements and analysis of the isothermal compressibility (C(s)(-1)), the mean area per molecule (A(12)), the excess free energy of mixing (DeltaG(Exc)) and the total free energy of mixing (DeltaG(M)). It has been found that the interactions between PAME and sterols are attractive; however, their strength is significantly weaker for mixtures of PAME with cholesterol than with ergosterol. Read More
Front Microbiol 2012 8;3:286. Epub 2012 Aug 8.
Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III Majadahonda, Madrid, Spain ; Group of Investigative Dermatology, University of Antioquia Medellín, Colombia.
"Amphotericin B acts through pore formation at the cell membrane after binding to ergosterol" is an accepted dogma about the action mechanism of this antifungal, and this sentence is widely found in the literature. But after 60 years of investigation, the action mechanism of Amphotericin B is not fully elucidated. Amphotericin B is a polyene substance that is one of the most effective drugs for the treatment of fungal and parasite infections. Read More