Antibacterial evaluations of thiazomycin- a potent thiazolyl peptide antibiotic from Amycolatopsis fastidiosa
- PMID: 17917239
- DOI: 10.1038/ja.2007.71
Antibacterial evaluations of thiazomycin- a potent thiazolyl peptide antibiotic from Amycolatopsis fastidiosa
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.
Similar articles
-
Isolation and structure elucidation of thiazomycin- a potent thiazolyl peptide antibiotic from Amycolatopsis fastidiosa.J Antibiot (Tokyo). 2007 Sep;60(9):554-64. doi: 10.1038/ja.2007.70. J Antibiot (Tokyo). 2007. PMID: 17917238
-
Isolation, structure, and antibacterial activity of thiazomycin A, a potent thiazolyl peptide antibiotic from Amycolatopsis fastidiosa.Bioorg Med Chem. 2008 Oct 1;16(19):8818-23. doi: 10.1016/j.bmc.2008.08.079. Epub 2008 Sep 6. Bioorg Med Chem. 2008. PMID: 18804380
-
Thiazomycins, thiazolyl peptide antibiotics from Amycolatopsis fastidiosa.J Nat Prod. 2009 May 22;72(5):841-7. doi: 10.1021/np800783b. J Nat Prod. 2009. PMID: 19334707
-
Key considerations in the treatment of complicated staphylococcal infections.Clin Microbiol Infect. 2008 Mar;14 Suppl 2:3-9. doi: 10.1111/j.1469-0691.2008.01923.x. Clin Microbiol Infect. 2008. PMID: 18226084 Review.
-
The use of daptomycin for Staphylococcus aureus infections in critical care medicine.Crit Care Clin. 2008 Apr;24(2):349-63, ix-x. doi: 10.1016/j.ccc.2007.12.010. Crit Care Clin. 2008. PMID: 18361950 Review.
Cited by
-
Bioactive heterocycles containing endocyclic N-hydroxy groups.Eur J Med Chem. 2015 Jun 5;97:505-24. doi: 10.1016/j.ejmech.2014.11.031. Epub 2014 Nov 18. Eur J Med Chem. 2015. PMID: 25466924 Free PMC article. Review.
-
Structural basis and dynamics of multidrug recognition in a minimal bacterial multidrug resistance system.Proc Natl Acad Sci U S A. 2014 Dec 23;111(51):E5498-507. doi: 10.1073/pnas.1412070111. Epub 2014 Dec 8. Proc Natl Acad Sci U S A. 2014. PMID: 25489067 Free PMC article.
-
Antibacterial and mechanism of action studies of boxazomycin A.J Antibiot (Tokyo). 2024 Oct;77(10):679-684. doi: 10.1038/s41429-024-00757-9. Epub 2024 Aug 1. J Antibiot (Tokyo). 2024. PMID: 39090325
-
tRNAs as antibiotic targets.Int J Mol Sci. 2014 Dec 25;16(1):321-49. doi: 10.3390/ijms16010321. Int J Mol Sci. 2014. PMID: 25547494 Free PMC article. Review.
-
Secondary Metabolites of the Genus Amycolatopsis: Structures, Bioactivities and Biosynthesis.Molecules. 2021 Mar 26;26(7):1884. doi: 10.3390/molecules26071884. Molecules. 2021. PMID: 33810439 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
