Francisella tularensis subsp. tularensis Induces a Unique Pulmonary Inflammatory Response: Role of Bacterial Gene Expression in Temporal Regulation of Host Defense Responses
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: kathie walters
PROVIDER: E-GEOD-44320 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:We used a shotgun proteomics approach to compare protein expression of antimicrobial resistant strains of Yersinia pestis and Francisella tularensis with paired antimicrobial sensitive strains. Biomass from both log phase and stationary phase growth were analyzed.
2022-01-24 | PXD029828 | Pride
Project description:Virulent Francisella tularensis induces a unique pulmonary inflammatory response characterized by temporal regulation of innate immune pathways correlating with altered bacterial gene expression patterns.
2013-04-15 | GSE44320 | GEO
Project description:Francisella tularensis may enter the body thorugh the lungs and cause fatal infection. In this study the inflammatory response to the virulent strain of Francisella (Schu4) was mapped over a 96h time-course using a custom microarray. Six groups of 4 mice were exposed to aerosolised Francisella tularensis and a three groups exposed to vehicle only control (media only). Following exposure mice were culled at 4 timepoints (1, 24, 48 and 96h). RNA was extracted and run on the custom array.
2011-03-01 | E-GEOD-17248 | biostudies-arrayexpress
Project description:Francisella tularensis is a category A select agent based on its infectivity and virulence but disease mechanisms in F. tularensis infection remain poorly understood. A murine pulmonary model of infection was therefore employed to characterize the host immune response to F. tularensis infection and to discern differences in responses to infection with the highly virulent Type A F. tularensis strain Schu4 and to the less virulent Type B live vaccine strain (LVS). Mice were infected intranasally with F. tularensis Schu4 or LVS and organ lesions were assessed 48 and 120 hours after infection. Experiments were also conducted to assess and compare the host immune response to infection using global transcriptional analysis. Mice were infected via low dose aerosol with F. tularensis Schu4 or LVS strains, and transcriptional response in the lungs and spleen was monitored using full mouse genome microarrays at 12, 24, 48, and 120 hours after infection. We found differential and temporal differences in expression of cytokine and chemokine genes, CD molecules, apoptosis, leukocytes and adhesion receptors, and immunological signaling between infection with Schu4 and LVS strains. The transcriptional differences coincided with marked differences in the timing and extent of organ lesions in mice infected with the LVS and Schu4 strains. Thus, these studies revealed both temporal and qualitative differences in the host immune response to infection with virulent F. tularensis Schu4 compared to infection with LVS.
2010-11-01 | GSE22203 | GEO
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
2010-05-19 | E-GEOD-12663 | biostudies-arrayexpress
Project description:We demonstrated recently that both constitutive and FAS-triggered apoptosis of human neutrophils are profoundly impaired by Francisella tularensis, but how this is achieved is largely unknown. To test the hypothesis that changes in neutrophil gene expression contribute to this phenotype, we used human oligonucleotide microarrays to identify differentially regulated genes in cells infected with F. tularensis strain LVS compared with uninfected controls. In order to examine the effect of F. tularensis on the neutrophil transcriptome, we performed microarray expression analysis on human neutrophils treated with F. tularensis subsp. holarctica live vaccine strain (LVS). Polymorphonuclear leukocytes (PMNs) were isolated from the blood of healthy donors. Control and F. tularensis-exposed PMNs were incubated at 37C for 0, 3, 6, 12, 24, and 48 hours.
2012-10-22 | E-GEOD-37416 | biostudies-arrayexpress
Project description:Francisella tularensis, is an extremely virulent bacterium that can be transmitted naturally by blood sucking arthropods. During mammalian infection, F. tularensis infects numerous types of host cells, including erythrocytes. As erythrocytes do not undergo phagocytosis or endocytosis, it remains unknown how F. tularensis invades these cells. Furthermore, the consequence of inhabiting the intracellular space of red blood cells has not been determined. Here, we provide evidence indicating that residing within an erythrocyte enhances the ability of F. tularensis to colonize ticks following a blood meal.
2017-05-24 | GSE93233 | GEO
Project description:Francisella tularensis is a category A select agent based on its infectivity and virulence but disease mechanisms in F. tularensis infection remain poorly understood. A murine pulmonary model of infection was therefore employed to characterize the host immune response to F. tularensis infection and to discern differences in responses to infection with the highly virulent Type A F. tularensis strain Schu4 and to the less virulent Type B live vaccine strain (LVS). Mice were infected intranasally with F. tularensis Schu4 or LVS and organ lesions were assessed 48 and 120 hours after infection. Experiments were also conducted to assess and compare the host immune response to infection using global transcriptional analysis. Mice were infected via low dose aerosol with F. tularensis Schu4 or LVS strains, and transcriptional response in the lungs and spleen was monitored using full mouse genome microarrays at 12, 24, 48, and 120 hours after infection. We found differential and temporal differences in expression of cytokine and chemokine genes, CD molecules, apoptosis, leukocytes and adhesion receptors, and immunological signaling between infection with Schu4 and LVS strains. The transcriptional differences coincided with marked differences in the timing and extent of organ lesions in mice infected with the LVS and Schu4 strains. Thus, these studies revealed both temporal and qualitative differences in the host immune response to infection with virulent F. tularensis Schu4 compared to infection with LVS. 18 mice total, 2 uninfected controls, 2 mice per time point, time points were 12 hour/24 hour/48 hour/ 120 hour post infection, 2 infection groups: LVS and Schu4 infection. Lung and spleen were harvested at each time point, poly A RNA was extracted, converted to cDNA, labeled and hybridized in triplicate
2010-11-01 | E-GEOD-22203 | biostudies-arrayexpress
Project description:This study was aimed to perform comparative expression analysis of both virulent and avirulent strains of F. tularensis with a goal to possibly identify genes unique to low and high virulent strains to understand their role, if any in virulence features of an isolate. Initially, thirty strains were selected representing both type A and type B clades of F. tularensis. Five strains failed to grow on Chamberlain's medium (Chamberlain 1965) and were excluded from the study. All the isolates were grown to mid-log phase in Chamberlain’s medium and the total RNA was collected by standard protocols for expression analysis. The samples were analyzed in duplicates. F. tularensis Schu S4, a known virulent strains was used as a reference strain for this study. Chamberlain RE (1965) "Evaluation of Live Tularemia Vaccine Prepared in a Chemically Defined Medium," Applied Microbiology, 13(2): 232-5
2011-02-28 | GSE26048 | GEO
Project description:Francisella tularensis is classified as a Category A priority pathogen and causes fatal disseminated disease in humans upon inhalation of less than 50 bacteria. Although drugs are available for treatment, they are not ideal because of toxicity and delivery, and in some cases relapse upon withdrawal. We have an ongoing program in the development of novel FabI enoyl-ACP-reductase enzyme inhibitors for Francisella and other select agents. To establish ftFabI in F. tularensis as a clinically relevant drug target, we demonstrated that the enzyme is essential for growth in vitro and that ftfabI is not transcriptionally altered in the presence of exogenous fatty acids. Inhibition of ftFabI results in loss of viability that is not rescued by exogenous fatty acids supplementation. Importantly, whole-genome transcriptional profiling of F. tularensis with DNA microarrays from infected tissues revealed that ftfabI and de novo fatty acid biosynthetic genes are transcriptionally active during infection. This is the first demonstration that the FabI enoyl-ACP-reductase enzyme encoded by F. tularensis is essential and that de novo fatty acid biosynthetic components are transcriptionally active during infection in the mouse model tularemia. 2 C57BL/6 mice were infected with Francisella tularensis strain Schu4 via the intranasal route. Spleen tissue was harvested at 120 hours post-infection and total RNA was isolated immediately after harvest. RNA was pooled and host polyA-tailed RNA and ribosomal RNA were depleted using hybridization probes coupled to magnetic beads. The resulting sample was enriched for bacterial mRNA, and dye labeled using random hexamer primed RT and Cy3-labeled dUTPs. Labeled cDNA was hybridized in triplicate to custom whole genome cDNA microarrays and scanned using a GenePix 4000B.
2012-08-03 | E-GEOD-39871 | biostudies-arrayexpress