In:
Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 48, No. 10 ( 2004-10), p. 3697-3701
Abstract:
Nocathiacins are cyclic thiazolyl peptides with inhibitory activity against gram-positive bacteria. BMS-249524 (nocathiacin I), identified from screening a library of compounds against a multiply antibiotic-resistant Enterococcus faecium strain, was used as a lead chemotype to obtain additional structurally related compounds. The MIC assay results of BMS-249524 and two more water-soluble derivatives, BMS-411886 and BMS-461996, revealed potent in vitro activities against a variety of gram-positive pathogens including methicillin-resistant Staphylococcus aureus , penicillin-resistant Streptococcus pneumoniae , vancomycin intermediate-resistant S. aureus , vancomycin-resistant enterococci, Mycobacterium tuberculosis and Mycobacterium avium . Analysis of killing kinetics revealed that these compounds are bactericidal for S. aureus with at least a 3-log 10 reduction of bacterial growth within 6 h of exposure to four times the MICs. Nocathiacin-resistant mutants were characterized by DNA sequence analyses. The mutations mapped to the rplK gene encoding the L11 ribosomal protein in the 50S subunit in a region previously shown to be involved in the binding of related thiazolyl peptide antibiotics. These compounds demonstrated potential for further development as a new class of antibacterial agents with activity against key antibiotic-resistant gram-positive bacterial pathogens.
Type of Medium:
Online Resource
ISSN:
0066-4804
,
1098-6596
DOI:
10.1128/AAC.48.10.3697-3701.2004
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2004
detail.hit.zdb_id:
1496156-8
SSG:
12
SSG:
15,3
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