LEGO-Lipophosphonoxin membrane activity is enhanced by presence of phosphatidylethanolamine but hindered by outer membrane
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00604452" target="_blank" >RIV/61388963:_____/25:00604452 - isvavai.cz</a>
Alternative codes found
RIV/61388955:_____/25:00604452 RIV/00216208:11310/25:10490818
Result on the web
<a href="https://doi.org/10.1038/s41598-024-83205-w" target="_blank" >https://doi.org/10.1038/s41598-024-83205-w</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41598-024-83205-w" target="_blank" >10.1038/s41598-024-83205-w</a>
Alternative languages
Result language
angličtina
Original language name
LEGO-Lipophosphonoxin membrane activity is enhanced by presence of phosphatidylethanolamine but hindered by outer membrane
Original language description
Finding effective antibiotics against multi-resistant strains of bacteria has been a challenging race. Linker-Evolved-Group-Optimized-Lipophosphonoxins (LEGO-LPPOs) are small modular synthetic antibacterial compounds targeting the cytoplasmic membrane. Here we focused on understanding the reasons for the variable efficacy of selected LEGO-LPPOs (LEGO-1, LEGO-2, LEGO-3, and LEGO-4) differing in hydrophobic and linker module structure and length. LEGO-1-4 permeabilized cytoplasmic membrane of Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and Escherichia coli, LEGO-1 with the longest linker module being the most effective. Gram-positive bacteria were more sensitive to LEGO-LPPO action compared to Gram-negatives, which was manifested as a delayed membrane permeabilization, higher minimal inhibitory concentration and lower amount of LEGO-LPPO bound to the cells. Outer membrane permeability measurements and time-kill assay showed that presence of the intact outer membrane brought about reduced susceptibility of Gram-negatives. Using liposome leakage and in silico simulations, we showed that membranes with major content of phosphatidylethanolamine were more prone to LEGO-LPPO permeabilization. The proposed mechanism stems from an electrostatic repulsion between highly positively charged LEGO-1 molecules and positively charged amino groups of phosphatidylethanolamine which destabilizes the membrane. Collectively, these data suggest that LEGO-LPPO membrane activity is enhanced by presence of phosphatidylethanolamine but hindered by presence of intact outer membrane.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10401 - Organic chemistry
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Scientific Reports
ISSN
2045-2322
e-ISSN
2045-2322
Volume of the periodical
15
Issue of the periodical within the volume
January
Country of publishing house
US - UNITED STATES
Number of pages
18
Pages from-to
1206
UT code for WoS article
001393111000026
EID of the result in the Scopus database
2-s2.0-85214393058