Gausemycin Antibiotic Family Acts via Ca2+-Dependent Membrane Targeting.
J Nat Prod
; 87(4): 664-674, 2024 Apr 26.
Article
em En
| MEDLINE
| ID: mdl-38362867
ABSTRACT
We report the molecular mechanism of action of gausemycins and the isolation of new members of the family, gausemycins C (1c), D (1d), E (1e), and F (1f), the minor components of the mixture. To elucidate the mechanism of action of gausemycins, we investigated the antimicrobial activity of the most active compounds, gausemycins A and B, in the presence of Ca2+, other metal ions, and phosphate. Gausemycins require a significantly higher Ca2+ concentration for maximum activity than daptomycin but lower than that required for malacidine and cadasides. Species-specific antimicrobial activity was found upon testing against a wide panel of Gram-positive bacteria. Membranoactivity of gausemycins was demonstrated upon their interactions with model lipid bilayers and micelles. The pore-forming ability was found to be dramatically dependent on the Ca2+ concentration and the membrane lipid composition. An NMR study of gausemycin B in zwitterionic and anionic micelles suggested the putative structure of the gausemycin/membrane complex and revealed the binding of Ca2+ by the macrocyclic domain of the antibiotic.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Testes de Sensibilidade Microbiana
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Cálcio
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Bactérias Gram-Positivas
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Antibacterianos
Idioma:
En
Revista:
J Nat Prod
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Federação Russa