Evidence map›Paper›PMID 39775141›Full record

ArticleScientific reports2025

LEGO-Lipophosphonoxin membrane activity is enhanced by presence of phosphatidylethanolamine but hindered by outer membrane.

Hana Brzobohatá, Milica Dugić, Viktor Mojr, Nitjawan Sahatsapan, Ivana Kóšiová, Tomáš Křížek, Tereza Dolejšová, Petra Lišková, Lukasz Cwiklik, Dominik Rejman and 2 more

Abstract read
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Hana BrzobohatáDepartment of Genetics and Microbiology, Faculty of Science, Charles University, Viničná 5, 128 00, Prague, Czech Republic.
Milica DugićDepartment of Genetics and Microbiology, Faculty of Science, Charles University, Viničná 5, 128 00, Prague, Czech Republic.
Viktor MojrInstitute of Organic Chemistry and Biochemistry, Czech Academy of Sciences v.v.i., Flemingovo náměstí 2, 166 10, Prague 6, Czech Republic.
Nitjawan SahatsapanInstitute of Organic Chemistry and Biochemistry, Czech Academy of Sciences v.v.i., Flemingovo náměstí 2, 166 10, Prague 6, Czech Republic.
Ivana KóšiováInstitute of Organic Chemistry and Biochemistry, Czech Academy of Sciences v.v.i., Flemingovo náměstí 2, 166 10, Prague 6, Czech Republic.
Tomáš KřížekDepartment of Analytical Chemistry, Faculty of Science, Charles University, Hlavova 8, 128 00, Prague, Czech Republic.
Tereza DolejšováDepartment of Genetics and Microbiology, Faculty of Science, Charles University, Viničná 5, 128 00, Prague, Czech Republic.
Petra LiškováDepartment of Genetics and Microbiology, Faculty of Science, Charles University, Viničná 5, 128 00, Prague, Czech Republic.
Lukasz CwiklikJ. Heyrovský Institute of Physical Chemistry, Czech Academy of Sciences v.v.i., Dolejškova 3, 182 23, Prague, Czech Republic.
Dominik RejmanInstitute of Organic Chemistry and Biochemistry, Czech Academy of Sciences v.v.i., Flemingovo náměstí 2, 166 10, Prague 6, Czech Republic. rejman@uochb.cas.cz.
Radovan FišerDepartment of Genetics and Microbiology, Faculty of Science, Charles University, Viničná 5, 128 00, Prague, Czech Republic. fiserr@natur.cuni.cz.
Gabriela MikušováDepartment of Genetics and Microbiology, Faculty of Science, Charles University, Viničná 5, 128 00, Prague, Czech Republic. seydlova@natur.cuni.cz.

Funding

Charles University Grant Agency 154024Czech Science Foundation 22-08857SEuropean Union-Next Generation EU LX22NPO5103
6 · The paper itself

Abstract

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.

Indexed as

Anti-Bacterial AgentsMicrobial Sensitivity TestsPhosphatidylethanolaminesBacterial Outer MembraneCell MembraneCell Membrane PermeabilityEscherichia coliStaphylococcus aureusAnti-Bacterial AgentsphosphatidylethanolaminePhosphatidylethanolamines

Identifiers

PMID39775141
PMCPMC11707287

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.