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dc.contributor.authorSchulz, Eilien
dc.contributor.authorGoes, Adriely
dc.contributor.authorGarcia, Ronald
dc.contributor.authorPanter, Fabian
dc.contributor.authorKoch, Marcus
dc.contributor.authorMüller, Rolf
dc.contributor.authorFuhrmann, Kathrin
dc.contributor.authorFuhrmann, Gregor
dc.date.accessioned2019-01-22T10:11:45Z
dc.date.available2019-01-22T10:11:45Z
dc.date.issued2018-11-28
dc.identifier.issn1873-4995
dc.identifier.pmid30292423
dc.identifier.doi10.1016/j.jconrel.2018.09.030
dc.identifier.urihttp://hdl.handle.net/10033/621665
dc.description.abstractUp to 25,000 people die each year from resistant infections in Europe alone, with increasing incidence. It is estimated that a continued rise in bacterial resistance by 2050 would lead up to 10 million annual deaths worldwide, exceeding the incidence of cancer deaths. Although the design of new antibiotics is still one way to tackle the problem, pharmaceutical companies investigate far less into new drugs than 30 years ago. Incorporation of antibiotics into nanoparticle drug carriers ("nanoantibiotics") is currently investigated as a promising strategy to make existing antibiotics regain antimicrobial strength and overcome certain types of microbial drug resistance. Many of these synthetic systems enhance the antimicrobial effect of drugs by protecting antibiotics from degradation and reducing their side effects. Nevertheless, they often cannot selectively target pathogenic bacteria and - due to their synthetic origin - may induce side-effects themselves. In this work, we present the characterisation of naturally derived outer membrane vesicles (OMVs) as biocompatible and inherently antibiotic drug carriers. We isolated OMVs from two representative strains of myxobacteria, Cystobacter velatus Cbv34 and Sorangiineae species strain SBSr073, a bacterial order with the ability of lysing other bacterial strains and currently investigated as sources of new secondary metabolites. We investigated the myxobacterias' inherent antibacterial properties after isolation by differential centrifugation and purification by size-exclusion chromatography. OMVs have an average size range of 145-194 nm. We characterised their morphology by electron cryomicroscopy and found that OMVs are biocompatible with epithelial cells and differentiated macrophages. They showed a low endotoxin activity comparable to those of control samples, indicating a low acute inflammatory potential. In addition, OMVs showed inherent stability under different storage conditions, including 4 °C, -20 °C, -80 °C and freeze-drying. OMV uptake in Gram-negative model bacterium Escherichia coli (E. coli) showed similar to better incorporation than liposome controls, indicating the OMVs may interact with model bacteria via membrane fusion. Bacterial uptake correlated with antimicrobial activity of OMVs as measured by growth inhibition of E. coli. OMVs from Cbv34 inhibited growth of E. coli to a comparable extent as the clinically established antibiotic gentamicin. Liquid-chromatography coupled mass spectrometry analyses revealed the presence of cystobactamids in OMVs, inhibitors of bacterial topoisomerase currently studied to treat different Gram-negative and Gram-positive pathogens. This work, may serve as an important basis for further evaluation of OMVs derived from myxobacteria as novel therapeutic delivery systems against bacterial infections.en_US
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectBiogenic drug carriersen_US
dc.subjectElectron cryomicroscopyen_US
dc.subjectExtracellular vesiclesen_US
dc.subjectMyxobacteriaen_US
dc.subjectNanoantibioticsen_US
dc.subjectOuter membrane vesiclesen_US
dc.titleBiocompatible bacteria-derived vesicles show inherent antimicrobial activity.en_US
dc.typeArticleen_US
dc.contributor.departmentHIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.en_US
dc.identifier.journalJournal of Controlled Releaseen_US
dc.source.journaltitleJournal of controlled release : official journal of the Controlled Release Society


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