Biocompatible bacteria-derived vesicles show inherent antimicrobial activity.

TLDR: The characterisation of naturally derived outer membrane vesicles (OMVs) as biocompatible and inherently antibiotic drug carriers and the presence of cystobactamids in OMVs may serve as an important basis for further evaluation of OMVs derived from myxobacteria as novel therapeutic delivery systems against bacterial infections.

About: This article is published in Journal of Controlled Release.The article was published on 2018-11-28 and is currently open access. It has received 73 citations till now. The article focuses on the topics: Antimicrobial & Bacteria.

Figures

Figure 1. Electron cryomicroscopy characterisation and size distribution of myxobacterial OMVs. a) OMVs were analysed by cryo-EM at different magnifications and are marked with arrows. Bright areas in the images indicate regions of lower transmission, small and big black spots in the SBSr073 samples are ice crystals as identified by their shape. b) Averaged spectra of size distribution of OMVs from Cbv34 and SBSr073 measured by nanoparticle tracking analysis after size exclusion chromatography purification and c) corresponding boxplot of average OMV sizes, Mean ± SD, n = 10.

Figure 3. Biocompatibility and endotoxin assessment of myxobacterial OMVs. Cell viability of Cbv34 and SBSr073 OMVs when incubated for 24 h with a) A549 epithelial cells and b) dTHP-1 macrophage cells, and lactate-dehydrogenase cytotoxicity assay of OMVs incubated for 24 h with c) A549 and d) dTHP-1 cells. Mean ± SD, n = 4–6. e) Representative light microscopy images of dTHP1 cells incubated for 24 h with Cbv34 OMVs, PBS (negative control) or Triton X (1%, positive control). f) Endotoxin activity of OMVs compared to control PBS collected from the SEC column under similar conditions. Cbv34 bacteria showed a lower concentration of endotoxins compared to E. coli when culturing samples with similar cell densities. Mean ± SD, n = 3, *p<0.05 (ANOVA followed by Tukey post-hoc test)

Figure 5. Inherent antibiotic effect of OMVs when incubated with E. coli. a) Incubation of Cbv34 OMVs (concentration 1011/mL) and SBSr073 OMVs (concentration 1010/mL) with E. coli and in comparison to free gentamicin (16 μg/mL). Mean ± SD, n = 3. b) Counting of colony-forming units of E. coli DH5-alpha incubated with different concentrations of Cbv34 OMVs. Mean ± SD, n = 3. c) Dose response curve of Cbv34 OMVs by incubating increasing concentrations of OMVs with E. coli.

Figure 2. Stability of myxobacterial OMVs upon different storage conditions. OMVs from Cbv34 and SBSr073 were isolated, purified, and stored for 7 and 75 days in PBS and under different conditions (4 °C, -20 °C, -80 °C, and after freeze-drying and at RT). a) Particle concentration of Cbv34 OMVs and b) evolution in size of Cbv34 OMVs, c) Particle concentration of SBSr073 OMVs,

Figure 4. Representative confocal fluorescence images of E. coli incubated with OMVs. E. coli