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Directed screen of Francisella novicida virulence determinants using Drosophila melanogaster
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik. (Computational Life Science Cluster (CLiC))
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
2010 (Engelska)Ingår i: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 78, nr 7, s. 3118-3128Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Francisella tularensis is a highly virulent, facultative intracellular human pathogen whose virulence mechanisms are not well understood. Occasional outbreaks of tularemia and the potential use of F. tularensis as a bioterrorist agent warrant better knowledge about the pathogenicity of this bacterium. Thus far, genome-wide in vivo screens for virulence factors have been performed in mice, all however restricted by the necessity to apply competition-based, negative-selection assays. We wanted to individually evaluate putative virulence determinants suggested by such assays and performed directed screening of 249 F. novicida transposon insertion mutants by using survival of infected fruit flies as a measure of bacterial virulence. Some 20% of the genes tested were required for normal virulence in flies; most of these had not previously been investigated in detail in vitro or in vivo. We further characterized their involvement in bacterial proliferation and pathogenicity in flies and in mouse macrophages. Hierarchical cluster analysis of mutant phenotypes indicated a functional linkage between clustered genes. One cluster grouped all but four genes of the Francisella pathogenicity island and other loci required for intracellular survival. We also identified genes involved in adaptation to oxidative stress and genes which might induce host energy wasting. Several genes related to type IV pilus formation demonstrated hypervirulent mutant phenotypes. Collectively, the data demonstrate that the bacteria in part use similar virulence mechanisms in mammals as in Drosophila melanogaster but that a considerable proportion of the virulence factors active in mammals are dispensable for pathogenicity in the insect model.

Ort, förlag, år, upplaga, sidor
ASM International, 2010. Vol. 78, nr 7, s. 3118-3128
Nyckelord [en]
tularensis subsp tularensis, disulfide bond formation, VI secretion, in vivo, schu S4, pathogenicity island, Escherichia coli, identification, mice, pathogenesis
Nationell ämneskategori
Mikrobiologi inom det medicinska området Infektionsmedicin Immunologi inom det medicinska området
Forskningsämne
mikrobiologi
Identifikatorer
URN: urn:nbn:se:umu:diva-38652DOI: 10.1128/IAI.00146-10ISI: 000278830200025PubMedID: 20479082OAI: oai:DiVA.org:umu-38652DiVA, id: diva2:379842
Tillgänglig från: 2010-12-20 Skapad: 2010-12-20 Senast uppdaterad: 2018-06-08Bibliografiskt granskad

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Åhlund, Monika KRydén, PatrikSjöstedt, AndersStöven, Svenja

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Åhlund, Monika KRydén, PatrikSjöstedt, AndersStöven, Svenja
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Institutionen för klinisk mikrobiologiInstitutionen för matematik och matematisk statistik
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Infection and Immunity
Mikrobiologi inom det medicinska områdetInfektionsmedicinImmunologi inom det medicinska området

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