Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of Franscisella tuarensis to identify new virulence factors utilized by F. tularensis which causes the zoonotic disease tularemia

ABSTRACT: The facultative intracellular bacterium Francisella tularensis causes the zoonotic disease tularemia. F. tularensis resides within host macrophages in vivo and this ability is essential for pathogenesis. The transcription factor MglA is required for expression of several Francisella genes that are necessary for replication in macrophages and for virulence in mice. We hypothesized that identification of MglA-regulated genes in the Francisella genome by transcriptional profiling of wild-type and mglA mutant bacteria would lead to the discovery of new virulence factors utilized by F. tularensis. One hundred and two MglA-regulated genes were identified, the majority of which were positively regulated, including all of the Francisella Pathogenicity Island (FPI) genes. We mutated novel MglA-regulated genes and tested the mutants for their ability to replicate and to induce cytotoxicity in macrophages, and to grow in mice. Mutants in MglA-regulated genes within the FPI (pdpB and cds2), as well as outside the FPI (FTT0989, oppB, and FTT1209c), were either attenuated or hypervirulent in macrophages as compared to the wild-type strain. All of these mutants exhibited decreased fitness in vivo in competition experiments with wild-type bacteria. We have identified 5 new Francisella virulence genes and our results suggest that characterization of additional MglA-regulated genes will yield further insights into the pathogenesis of this bacterium.

ORGANISM(S): Francisella tularensis

SUBMITTER: Janos Demeter

PROVIDER: E-SMDB-3741 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Identification of MglA-regulated genes reveals novel virulence factors in Francisella tularensis.

Brotcke Anna A Weiss David S DS Kim Charles C CC Chain Patrick P Malfatti Stephanie S Garcia Emilio E Monack Denise M DM

Infection and immunity 20060925 12

The facultative intracellular bacterium Francisella tularensis causes the zoonotic disease tularemia. F. tularensis resides within host macrophages in vivo, and this ability is essential for pathogenesis. The transcription factor MglA is required for the expression of several Francisella genes that are necessary for replication in macrophages and for virulence in mice. We hypothesized that the identification of MglA-regulated genes in the Francisella genome by transcriptional profiling of wild-t ...[more]

PMID: 17000729

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Project description:The highly infectious bacterium Francisella tularensis is a facultative intracellular pathogen, whose virulence requires proliferation inside host cells, including macrophages. Although some Francisella determinants of intracellular growth have been identified, much remains to be understood about the pathogenesis of this organism. In particular, how Francisella responds to its intracellular environment could provide clues about its intracellular biology and reveal pathogenic determinants based on their intracellular expression profiles. Here we have performed a global transcriptional profiling of the highly virulent F. tularensis subsp. tularensis Schu S4 strain during its intracellular cycle within primary murine macrophages. Phagocytosed bacteria rapidly responded to their intracellular environment and progressively altered their transcriptional profile over time. Differential gene expression profiles were revealed that correlated with specific intracellular locations of the bacteria. Upregulation of general and oxidative stress response genes was a hallmark of the early phagosomal and late endosomal stages, while induction of a subset of transport and metabolic genes characterized the cytosolic replication stages. Expression of the Francisella Pathogenicity Island (FPI) genes, the functions of which are associated with intracellular proliferation, increased during the intracellular cycle. Similarly, 27 chromosomal loci putatively encoding hypothetical, secreted, outer membrane proteins or transcriptional regulators were identified as upregulated during the intracellular cycle. In-frame deletion of FTT0383, the Schu S4 ortholog of fevR, of FTT0369c or FTT1676 abolished the ability of Schu S4 to either survive or proliferate intracellularly, demonstrating that bacterial factors of intracellular pathogenesis can be identified based on their intracellular expression profile. In conclusion, establishing the intracellular transcriptome of Francisella has revealed important aspects of its intracellular biology and identified novel virulence determinants of this pathogen. Keywords: Time series Intracellular cycle within primary murine macrophages using the time series of zero, one, two, four, eight, twelve, sixteen and twenty-four hours

Dataset Information

Transcription profiling of Franscisella tuarensis to identify new virulence factors utilized by F. tularensis which causes the zoonotic disease tularemia

Publications

Identification of MglA-regulated genes reveals novel virulence factors in Francisella tularensis.

Similar Datasets

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