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dc.contributor.authorGoes, Adriely
dc.contributor.authorLapuhs, Philipp
dc.contributor.authorKuhn, Thomas
dc.contributor.authorSchulz, Eilien
dc.contributor.authorRichter, Robert
dc.contributor.authorPanter, Fabian
dc.contributor.authorDahlem, Charlotte
dc.contributor.authorKoch, Marcus
dc.contributor.authorGarcia, Ronald
dc.contributor.authorKiemer, Alexandra K
dc.contributor.authorMüller, Rolf
dc.contributor.authorFuhrmann, Gregor
dc.identifier.citationCells. 2020 Jan 12;9(1). pii: cells9010194. doi: 10.3390/cells9010194.en_US
dc.description.abstractIn 2019, it was estimated that 2.5 million people die from lower tract respiratory infections annually. One of the main causes of these infections is Staphylococcus aureus, a bacterium that can invade and survive within mammalian cells. S. aureus intracellular infections are difficult to treat because several classes of antibiotics are unable to permeate through the cell wall and reach the pathogen. This condition increases the need for new therapeutic avenues, able to deliver antibiotics efficiently. In this work, we obtained outer membrane vesicles (OMVs) derived from the myxobacteria Cystobacter velatus strain Cbv34 and Cystobacter ferrugineus strain Cbfe23, that are naturally antimicrobial, to target intracellular infections, and investigated how they can affect the viability of epithelial and macrophage cell lines. We evaluated by cytometric bead array whether they induce the expression of proinflammatory cytokines in blood immune cells. Using confocal laser scanning microscopy and flow cytometry, we also investigated their interaction and uptake into mammalian cells. Finally, we studied the effect of OMVs on planktonic and intracellular S. aureus. We found that while Cbv34 OMVs were not cytotoxic to cells at any concentration tested, Cbfe23 OMVs affected the viability of macrophages, leading to a 50% decrease at a concentration of 125,000 OMVs/cell. We observed only little to moderate stimulation of release of TNF-alpha, IL-8, IL-6 and IL-1beta by both OMVs. Cbfe23 OMVs have better interaction with the cells than Cbv34 OMVs, being taken up faster by them, but both seem to remain mostly on the cell surface after 24 h of incubation. This, however, did not impair their bacteriostatic activity against intracellular S. aureus. In this study, we provide an important basis for implementing OMVs in the treatment of intracellular infections.en_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.subjectStaphylococcus aureusen_US
dc.subjectantimicrobial resistanceen_US
dc.subjectbiogenic drug carriersen_US
dc.subjectextracellular vesiclesen_US
dc.subjectintracellular infectionen_US
dc.subjectouter membrane vesiclesen_US
dc.titleMyxobacteria-Derived Outer Membrane Vesicles: Potential Applicability Against Intracellular Infections.en_US
dc.contributor.departmentHIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.en_US

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