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Tyrothricin is a topical antibiotic with broad spectrum activity against Gram positive bacteria and some fungal infections.
Tyrothricin is a topical antibiotic with broad spectrum activity against Gram positive bacteria and some fungal infections.
Tyrocidines have a β-sheet structure containing both L and D amino acids . These structural features contribute to the formation of a curved dimer in which most amino acid side chains are located on the convex surface. The dimer orients itself at the membrane-water interface on bacterial cells with the relatively hydrophilic back-bone on the concave side facing the external environment and the many hydrophobic side chains on the convex side facing into the cell's lipid bilayer. The tyrocidine dimer is able to disrupt the cell membrane producing leakage of cell contents but the exact mechanism of this permeabilization is unclear. Tyrocidines appear to act as reversible non-competitive inhibitors of acetylcholinesterase and β-galactosidase . The relation of this to their antibacterial action is unknown. Gramcidins adopt similar β-sheet structures but are capable of forming β-helices . They can either form a double helix, running either parallel or anti-parallel, or a helical dimer wherein the N-termini of each polypeptide meets in the middle of the lipid bilayer. The alternating L and D amino acid structure allows the hydrophobic side chains to point outwards into the lipid bilayer, leaving the more hydrophilic backbone to form the lumen of the pore. The carbonyl oxygen atoms aid in the transport of cations through the pore. In both double helix and helical dimer conformations, gramcidins are capable of transporting monovalent cations through the membrane. Divalent cations result in blockage of the pore or channel when bound. Loss of potassium ions through membrane permeabilization seems to inhibit bacterial growth. Gramcidin also appears to be able to insert into the mitochondial membrane and conduct hydrogen ions . This results in an uncoupling of oxidative phosphorylation from ATP generation due to the loss of the hydrogen ion gradient necessary for H+ATPase function.
Tyrothricin is used as an over the counter topical antibiotic.
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