Intracellular biology and virulence determinants ofFrancisella tularensisrevealed by transcriptional profiling inside macrophages
| Autor: | Vinod Nair, Jean Celli, Deborah D. Crane, John J. Kupko, Dan E. Sturdevant, Tara D. Wehrly, Craig Martens, Dedeke Brouwer, Elizabeth R. Fischer, Kimmo Virtaneva, Audrey Chong, Luke Wicke, Jessica A. Edwards, Robert Child, Alissa J. Curda, Stephen F. Porcella, Catharine M. Bosio |
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| Rok vydání: | 2009 |
| Předmět: |
Genomic Islands
Virulence Factors Molecular Sequence Data Immunology Virulence Endosomes Microbiology Article Mice Cytosol Stress Physiological Phagosomes Virology Animals Francisella tularensis Pathogen Cells Cultured Oligonucleotide Array Sequence Analysis biology Gene Expression Profiling Macrophages Intracellular parasite Biological Transport biology.organism_classification Pathogenicity island Molecular biology Cell biology Mice Inbred C57BL Gene expression profiling Oxidative Stress Genes Bacterial Francisella Intracellular |
| Zdroj: | Cellular Microbiology. 11:1128-1150 |
| ISSN: | 1462-5822 1462-5814 |
| DOI: | 10.1111/j.1462-5822.2009.01316.x |
| Popis: | Summary The highly infectious bacterium Francisella tularensis is a facultative intracellular pathogen, whose virulence requires proliferation inside host cells, including macrophages. Here we have performed a global transcriptional profiling of the highly virulent F. tularensis ssp. tularensis Schu S4 strain during its intracellular cycle within primary murine macrophages, to characterize its intracellular biology and identify pathogenic determinants based on their intracellular expression profiles. Phagocytosed bacteria rapidly responded to their intracellular environment and subsequently altered their transcriptional profile. Differential gene expression profiles were revealed that correlated with specific intracellular locale 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 transport and metabolic genes characterized the cytosolic replication stage. Expression of the Francisella Pathogenicity Island (FPI) genes, which are required for intracellular proliferation, increased during the intracellular cycle. Similarly, 27 chromosomal loci encoding putative hypothetical, secreted, outer membrane proteins or transcriptional regulators were identified as upregulated. Among these, deletion of FTT0383, FTT0369c or FTT1676 abolished the ability of Schu S4 to survive or proliferate intracellularly and cause lethality in mice, therefore identifying novel determinants of Francisella virulence from their intracellular expression profile. |
| Databáze: | OpenAIRE |
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