Fungal infections, polyene antibiotics

Amphotericin B, is a polyene antibiotic, used in the therapy of systemic fungal infections. Its mode of action exploits differences in membrane composition between the pathogen and the human host. Ergosterol, the predominant sterol of fungi, plants, and some protozoan parasites, interacts with Amphotericin B, resulting in an increased ion permeability of the membrane. Humans contain cholesterol, which has a low affinity for amphotericin B. 

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. 

Amphotericin B, a polyene antibiotic used for deep fungal infection... 

Amphotericin B (AmB) a polyene macrolide antibiotic with strong activity against a broad spectrum of fungal infections has long been identified as nephrotoxic. The toxic mechanism is assumed to be that binding of AmB to sterols in the cell membrane results in the formation of aqueous pores, which leads to a dis-regulation of volume and ion concentrations within the cells [216]. However, Hsu et al. postulated by using... 

Systemic fungal diseases (e.g. histoplasmosis and blastomycosis) are uncommon but, if untreated, often fatal. They usually take the form of lung infections or meningitis. The best treatment is still the polyene antibiotic, amphotericin B 5.14) whose mode of action is described in Section 5.4.1 (p. 192). It is usually administered intravenously. Flucytosine 4.23) is an excellent synergist (Section 4.0, p. 131), seldom given alone. Intravenous miconazole 6.23) provides alternative therapy, but there are frequent adverse reactions. An orally active analogue, ketoconazole ( Nizoral ) was introduced in 1981, and looks promising. 

The discovery of the polyene antibiotics, isolated from species of Streptomyces, found in soils about 1950, ushered in a treatment for systemic fungal infections that was biochemically unique (Dutcher, Boyak and Fox, 1954). 

Until recently, polyene antibiotics were used as antifungal agents, but several func> lions have been now assigned to polyenes such as iromunostimulatory dnigs, insecticides, application in AIDS-related fungal infections, and so forth (see SectkHi V). 

A group of antibiotics that are produced by Streptomyces spp. contain polyene groupings. These antibiotics inhibit the growth of certain fungi and some of them have proved effective against fungal infections in man. 

Any selectively in the action of polyene antiobiotics in eukaryotes must be based on the differing affinities of polyenes for individual sterols. The use of amphotericin B as a drug in the treatment of mycotic infections in man is indicative of the apparently greater affinity of the antibiotic for the fungal sterol ergosterol rather than for the mammalian sterol cholesterol. 

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