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Directed screen of Francisella novicida virulence determinants using Drosophila melanogaster
Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics. (Computational Life Science Cluster (CLiC))
Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
2010 (English)In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 78, no 7, 3118-3128 p.Article in journal (Refereed) 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.

Place, publisher, year, edition, pages
ASM International, 2010. Vol. 78, no 7, 3118-3128 p.
Keyword [en]
tularensis subsp tularensis, disulfide bond formation, VI secretion, in vivo, schu S4, pathogenicity island, Escherichia coli, identification, mice, pathogenesis
National Category
Microbiology in the medical area Infectious Medicine Immunology in the medical area
Research subject
URN: urn:nbn:se:umu:diva-38652DOI: 10.1128/IAI.00146-10ISI: 000278830200025PubMedID: 20479082OAI: diva2:379842
Available from: 2010-12-20 Created: 2010-12-20 Last updated: 2015-10-20Bibliographically approved

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Åhlund, Monika KRydén, PatrikSjöstedt, AndersStöven, Svenja
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