Polyene membrane disrupters

Polyene Membrane Disrupters—Amphotericin B, Nystatin, and Congeners... 

Cytoplasmic membrane Polymyxins Polyenes Imidazoles and triazoles Naftidine Disrupt bacterial membranes Disrupt fungal membranes Inhibit ergosterol synthesis Inhibits ergosterol synthesis Bind to LPS and phospholipids Bind preferentially to ergosterol Pathway not in mammalian cells Pathway not in mammalian cells... 

How do antibiotics act Some, like penicillin, block specific enzymes. Peptide antibiotics often form complexes with metal ions (Fig. 8-22) and disrupt the control of ion permeability in bacterial membranes. Polyene antibiotics interfere with proton and ion transport in fungal membranes. Tetracyclines and many other antibiotics interfere directly with protein synthesis (Box 29-B). Others intercalate into DNA molecules (Fig. 5-23 Box 28-A). There is no single mode of action. The search for suitable antibiotics for human use consists in finding compounds highly toxic to infective organisms but with low toxicity to human cells. 

Disruption of cell membrane function Azole and polyene antifungal agents... 

Antifungal polyene drug of choice for some systemic mycoses binds to er-gosterol to disrupt fungal cell membrane permeability. Tox chills and fever, hypotension, nephrotoxicity (dose-limiting less with liposomal forms). 

The polyenes have an affinity for sterol-containing membranes, insert into the membranes, and disrupt membrane functions. 

The stability of bilayers in the presence of polyene antibiotics has been investigated [199]. Pure lecithin bilayers were found to be stable in the presence of 40 /xM filipin or nystatin in contrast, bilayers consisting of equal parts cholesterol and lecithin were disrupted rapidly by filipin but considerably more slowly by nystatin. Bilayers consisting exclusively of cholesterol or bilayers with phospholipid sterol ratios of 10 1 were stable in the presence of filipin. When added to a sterol-containing lecithin bilayer, filipin removed the sterol from the membrane by non-polar association, changing the fluidity of the lipid chains in the bilayer, and ultimately caused membrane breakdown [200],... 

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