ArticleJournal of extracellular vesicles2024
Lipid A in outer membrane vesicles shields bacteria from polymyxins.
Article in Journal of extracellular vesicles, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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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.
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Who cites it
13 citing papers in PubMed.
- Probiotic extracellular vesicles reprogram macrophage immunometabolism: From gut crosstalk to host health.Gut microbes · 2026Review
- Harnessing generative AI for predicting and optimizing antimicrobial peptides against drug-resistant infections.npj antimicrobials and resistance · 2026Article
- Mechanistic insights into the inhibitory effects of eukaryotically expressed Sarcotoxin II 50 onMicrobiology spectrum · 2026Article
- Socio-evolutionary role of bacterial membrane vesicles in cooperation and competition within microbial communities.The ISME journal · 2026Review
- Bioengineering modification and application of bacterial outer membrane vesicles.International journal of medical sciences · 2026Review
- Bacterial extracellular vesicles as multifaceted regulators of human diseases and emerging therapeutic platforms.Theranostics · 2026Review
- Neutrophil-mediated delivery of hybrid cross-species nanovesicles for treatment of bacterial infections.Nature communications · 2025Article
- Microbial membrane vesicles and the intestinal epithelium: a crosstalk in health and disease.Archives of microbiology · 2025Review
- Extracellular defense of bacteria against antimicrobial peptides.Journal of bacteriology · 2025Review
- The role and mechanism of bacterial outer membrane vesicles in the development of periodontitis.Frontiers in microbiology · 2025Review
- Research progress on bacterial outer membrane vesicles in antibiotic resistance and clinical anti-infective therapy.Frontiers in microbiology · 2025Review
- Assessment of the reproducibility of bacterial membrane vesicle isolation and characterization.Extracellular vesicles and circulating nucleic acids · 2025Article
- Lipid A in outer membrane vesicles shields bacteria from polymyxins.Journal of extracellular vesicles · 2024Article
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Authors and funding
20 authors.
Funding
Abstract
The continuous emergence of multidrug-resistant bacterial pathogens poses a major global healthcare challenge, with Klebsiella pneumoniae being a prominent threat. We conducted a comprehensive study on K. pneumoniae's antibiotic resistance mechanisms, focusing on outer membrane vesicles (OMVs) and polymyxin, a last-resort antibiotic. Our research demonstrates that OMVs protect bacteria from polymyxins. OMVs derived from Polymyxin B (PB)-stressed K. pneumoniae exhibited heightened protective efficacy due to increased vesiculation, compared to OMVs from unstressed Klebsiella. OMVs also shield bacteria from different bacterial families. This was validated ex vivo and in vivo using precision cut lung slices (PCLS) and Galleria mellonella. In all models, OMVs protected K. pneumoniae from PB and reduced the associated stress response on protein level. We observed significant changes in the lipid composition of OMVs upon PB treatment, affecting their binding capacity to PB. The altered binding capacity of single OMVs from PB stressed K. pneumoniae could be linked to a reduction in the lipid A amount of their released vesicles. Although the amount of lipid A per vesicle is reduced, the overall increase in the number of vesicles results in an increased protection because the sum of lipid A and therefore PB binding sites have increased. This unravels the mechanism of the altered PB protective efficacy of OMVs from PB stressed K. pneumoniae compared to control OMVs. The lipid A-dependent protective effect against PB was confirmed in vitro using artificial vesicles. Moreover, artificial vesicles successfully protected Klebsiella from PB ex vivo and in vivo. The findings indicate that OMVs act as protective shields for bacteria by binding to polymyxins, effectively serving as decoys and preventing antibiotic interaction with the cell surface. Our findings provide valuable insights into the mechanisms underlying antibiotic cross-protection and offer potential avenues for the development of novel therapeutic interventions to address the escalating threat of multidrug-resistant bacterial infections.
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Registered trials
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.