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Whiteley, L; Meffert, T; Haug, M; Weidenmaier, C; Hopf, V; Bitschar, K; Schittek, B; Kohler, C; Steinmetz, I; West, TE; Schwarz, S.
Entry, Intracellular Survival, and Multinucleated-Giant-Cell-Forming Activity of Burkholderia pseudomallei in Human Primary Phagocytic and Nonphagocytic Cells.
Infect Immun. 2017; 85(10): Doi: 10.1128/IAI.00468-17 [OPEN ACCESS]
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Co-Autor*innen der Med Uni Graz
Steinmetz Ivo
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Abstract:
The human pathogenBurkholderia pseudomalleiand the related speciesBurkholderia thailandensisare facultative intracellular bacteria characterized by the ability to escape into the cytosol of the host cell and to stimulate the formation of multinucleated giant cells (MNGCs). MNGC formation is induced via an unknown mechanism by bacterial type VI secretion system 5 (T6SS-5), which is an essential virulence factor in both species. Despite the vital role of the intracellular life cycle in the pathogenesis of the bacteria, the range of host cell types permissive for initiation and completion of the intracellular cycle is poorly defined. In the present study, we used several different types of human primary cells to evaluate bacterial entry, intracellular survival, and MNGC formation. We report the capacity ofB. pseudomalleito enter, efficiently replicate in, and mediate MNGC formation of vein endothelial and bronchial epithelial cells, indicating that the T6SS-5 is important in the host-pathogen interaction in these cells. Furthermore, we show thatB. pseudomalleiinvades fibroblasts and keratinocytes and survives inside these cells as well as in monocyte-derived macrophages and neutrophils for at least 17 h postinfection; however, MNGC formation is not induced in these cells. In contrast, infection of mixed neutrophils and RAW264.7 macrophages withB. thailandensisstimulated the formation of heterotypic MNGCs in a T6SS-5-dependent manner. In summary, the ability of the bacteria to enter and survive as well as induce MNGC formation in certain host cells may contribute to the pathogenesis observed inB. pseudomalleiinfection. Copyright © 2017 American Society for Microbiology.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Bronchi - cytology
Bronchi - microbiology
Burkholderia pseudomallei - growth & development
Burkholderia pseudomallei - pathogenicity
Burkholderia pseudomallei - physiology
Cell Line -
Cells, Cultured -
Cytosol - microbiology
Endothelial Cells - microbiology
Epithelial Cells - microbiology
Fibroblasts - microbiology
Giant Cells - microbiology
Host-Pathogen Interactions -
Humans -
Keratinocytes - microbiology
Macrophages - microbiology
Mice -
Neutrophils - microbiology
Phagocytes - microbiology
Type VI Secretion Systems - metabolism
Virulence -

Find related publications in this database (Keywords)
Burkholderia pseudomallei
primary cells
type VI secretion system
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