Gausemycin Antibiotic Family Acts via Ca 2+ -Dependent Membrane Targeting.

Autor: Kravchenko TV; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997 Moscow, Russia.; Gause Institute of New Antibiotics, B. Pirogovskaya 11, 119021 Moscow, Russia., Paramonov AS; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997 Moscow, Russia., Kudzhaev AM; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997 Moscow, Russia., Efimova SS; Institute of Cytology of the Russian Academy of Sciences, Tikhoretsky Prospect 4, 194064 St. Petersburg, Russia., Khorev AS; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997 Moscow, Russia., Kudryakova GK; Gause Institute of New Antibiotics, B. Pirogovskaya 11, 119021 Moscow, Russia., Ivanov IA; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997 Moscow, Russia., Chistov AA; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997 Moscow, Russia., Baranova AA; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997 Moscow, Russia., Krasilnikov MS; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997 Moscow, Russia.; Department of Chemistry, Lomonosov Moscow State University, 1-3 Leninskie Gory, 119992 Moscow, Russia., Lapchinskaya OA; Gause Institute of New Antibiotics, B. Pirogovskaya 11, 119021 Moscow, Russia., Tyurin AP; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997 Moscow, Russia., Ostroumova OS; Institute of Cytology of the Russian Academy of Sciences, Tikhoretsky Prospect 4, 194064 St. Petersburg, Russia., Smirnov IV; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997 Moscow, Russia., Terekhov SS; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997 Moscow, Russia., Dontsova OA; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997 Moscow, Russia.; Department of Chemistry, Lomonosov Moscow State University, 1-3 Leninskie Gory, 119992 Moscow, Russia., Shenkarev ZO; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997 Moscow, Russia., Alferova VA; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997 Moscow, Russia., Korshun VA; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997 Moscow, Russia.
Jazyk: angličtina
Zdroj: Journal of natural products [J Nat Prod] 2024 Apr 26; Vol. 87 (4), pp. 664-674. Date of Electronic Publication: 2024 Feb 16.
DOI: 10.1021/acs.jnatprod.3c00612
Abstrakt: 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 Ca 2+ , other metal ions, and phosphate. Gausemycins require a significantly higher Ca 2+ 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 Ca 2+ 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 Ca 2+ by the macrocyclic domain of the antibiotic.
Databáze: MEDLINE
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