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  • Title: Antibacterial evaluations of thiazomycin- a potent thiazolyl peptide antibiotic from Amycolatopsis fastidiosa.
    Author: Singh SB, Occi J, Jayasuriya H, Herath K, Motyl M, Dorso K, Gill C, Hickey E, Overbye KM, Barrett JF, Masurekar P.
    Journal: J Antibiot (Tokyo); 2007 Sep; 60(9):565-71. PubMed ID: 17917239.
    Abstract:
    Thiazomycin is a novel thiazolyl peptide closely related to nocathiacin I. It was isolated from Amycolatopsis fastidiosa by chemical and biological screening. Thiazomycin showed highly potent bactericidal activity against Gram-positive pathogens (MIC range 0.002 approximately 0.064 microg/ml) and did not show cross-resistance to clinically relevant antibiotic classes such as beta-lactams, vancomycin, oxazolidinone and quinolones. It was highly efficacious against Staphylococcus aureus infection in mice exhibiting an ED(99) value of 0.15 mg/kg by subcutaneous administration. It inhibited bacterial growth by selective inhibition of protein synthesis and it was thought to interact with L11 protein and 23S rRNA of the 50S ribosome. Structurally, it possesses an oxazolidine ring in the amino-sugar residue that provides further opportunities for selective chemical modifications that are not feasible with other thiazolyl peptides. More importantly such a modification can potentially lead to semi-synthetic compounds that overcome problems that have hampered clinical development of this class of compounds. Despite its positive attributes, emergence of an unacceptable frequency of resistance poses significant challenges for further development of thiazomycin and this class of molecules for therapeutic use.
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