Myxobacteria-Derived Outer Membrane Vesicles: Potential Applicability Against Intracellular Infections
Adriely Goes,
Philipp Lapuhs,
Thomas Kuhn,
Eilien Schulz,
Robert Richter,
Fabian Panter,
Charlotte Dahlem,
Marcus Koch,
Ronald Garcia,
Alexandra K. Kiemer,
Rolf Müller,
Gregor Fuhrmann
Affiliations
Adriely Goes
Helmholtz Centre for Infection Research (HZI), Biogenic Nanotherapeutics Group (BION), Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Campus E8.1, 66123 Saarbrücken, Germany
Philipp Lapuhs
Helmholtz Centre for Infection Research (HZI), Biogenic Nanotherapeutics Group (BION), Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Campus E8.1, 66123 Saarbrücken, Germany
Thomas Kuhn
Helmholtz Centre for Infection Research (HZI), Biogenic Nanotherapeutics Group (BION), Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Campus E8.1, 66123 Saarbrücken, Germany
Eilien Schulz
Helmholtz Centre for Infection Research (HZI), Biogenic Nanotherapeutics Group (BION), Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Campus E8.1, 66123 Saarbrücken, Germany
Robert Richter
Department of Pharmacy, Saarland University, Campus Building E8.1, 66123 Saarbrücken, Germany
Fabian Panter
Helmholtz Centre for Infection Research (HZI), Department of Microbial Natural Products (MINS), Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Campus E8.1, 66123 Saarbrücken, Germany
Charlotte Dahlem
Department of Pharmacy, Pharmaceutical Biology, Saarland University, 66123 Saarbrücken, Germany
Marcus Koch
INM-Leibniz Institute for New Materials, Campus D2 2, 66123 Saarbrücken, Germany
Ronald Garcia
Helmholtz Centre for Infection Research (HZI), Department of Microbial Natural Products (MINS), Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Campus E8.1, 66123 Saarbrücken, Germany
Alexandra K. Kiemer
Department of Pharmacy, Pharmaceutical Biology, Saarland University, 66123 Saarbrücken, Germany
Rolf Müller
Department of Pharmacy, Saarland University, Campus Building E8.1, 66123 Saarbrücken, Germany
Gregor Fuhrmann
Helmholtz Centre for Infection Research (HZI), Biogenic Nanotherapeutics Group (BION), Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Campus E8.1, 66123 Saarbrücken, Germany
In 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.
