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AR-13, a celecoxib derivative, directly kills Francisella in vitro and aids clearance and mouse survival in vivo

ABSTRACT: The goal of this study is to compare transcriptomics between wild type LVS vs AR-13 isogenic resistant mutant

ORGANISM(S): Francisella tularensis subsp. holarctica LVS

PROVIDER: GSE100069 | GEO | 2017/06/19

SECONDARY ACCESSION(S): PRJNA390627

REPOSITORIES: GEO

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AR-13, a Celecoxib Derivative, Directly Kills <i>Francisella In Vitro</i> and Aids Clearance and Mouse Survival <i>In Vivo</i>.

Project description:Francisella tularensis (F. tularensis) is the causative agent of tularemia and is classified as a Tier 1 select agent. No licensed vaccine is currently available in the United States and treatment of tularemia is confined to few antibiotics. In this study, we demonstrate that AR-13, a derivative of the cyclooxygenase-2 inhibitor celecoxib, exhibits direct in vitro bactericidal killing activity against Francisella including a type A strain of F. tularensis (SchuS4) and the live vaccine strain (LVS), as well as toward the intracellular proliferation of LVS in macrophages, without causing significant host cell toxicity. Identification of an AR-13-resistant isolate indicates that this compound has an intracellular target(s) and that eﬄux pumps can mediate AR-13 resistance. In the mouse model of tularemia, AR-13 treatment protected 50% of the mice from lethal LVS infection and prolonged survival time from a lethal dose of F. tularensis SchuS4. Combination of AR-13 with a sub-optimal dose of gentamicin protected 60% of F. tularensis SchuS4-infected mice from death. Taken together, these data support the translational potential of AR-13 as a lead compound for the further development of new anti-Francisella agents.

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Project description:LVS iclR deletion mutant vs. wild-type LVS

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Transcription profiling of wild type and relA spoT mutant Francisella tularensis

Project description:Global gene expression profile in an LVS relA spoT mutant compared to wild-type LVS

2010-01-01 | E-MEXP-1818 | biostudies-arrayexpress

Gene expression profiling in Nlrp3 deficient mice infected with Francisella tularensis

Project description:This study investigated gene expression profile in wild type and nlrp3 deficient mice infected with F. tularensis LVS. RNA-sequencing was performed to determine the transcript levels of genes using total RNA extracted from lungs of wild type C57BL/6 and Nlrp3-/- mice infected with 1 × 104 CFU of F. tularensis LVS on days 3 and 7 post-infection.

2021-10-13 | GSE183003 | GEO

Novel Small RNA Modulates Virulence in Francisella tularensis

Project description:Most sRNAs control the expression of target genes by interacting with their mRNA. The fvr1 (Francisella virulence RNA 1) gene is found in the IGR between FTL_0777 and FTL_0778 and its sequence does not overlap those of the flanking genes, indicating that its target(s) is located in trans. Base-pairing between a sRNA and target mRNA generally leads to changed translation and often the stability of the mRNA is affected as well. Therefore, to identify possible targets of Fvr1, we compared the transcriptomes of the LVS?fvr1(LVS, for Live Vaccine Strain) and LVS/pfvr1+ strains after growth in liquid broth.

2012-01-31 | E-MEXP-3424 | biostudies-arrayexpress

Transcription profiling of Francisella tularensis LVS caiC mutant compared to wild-type LVS

Project description:Global gene expression profile of an LVS caiC mutant compared to wild-type LVS

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Transcription profiling of Francisella tularensis LVS trmE mutant compared to wild-type LVS

Project description:Global gene expression profile of an LVS trmE mutant compared to wild-type LVS

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Transcription profiling of Francisella tularensis LVS cphA mutant compared to wild-type LVS

Project description:Global gene expression profile of an LVS cphA mutant compared to wild-type LVS

2010-01-01 | E-MEXP-2328 | biostudies-arrayexpress

Transcription profiling of Francisella tularensis LVS mglA mutant compared to wild-type LVS

Project description:Global gene expression profile of an LVS mglA mutant compared to wild-type LVS

2010-01-01 | E-MEXP-2330 | biostudies-arrayexpress

Expression data from multiple strains of Francisella

Project description:Comparison of expression profiles of strains of Francisella to identify virulence factors We used custom microarrays to detail the global gene expression of four strains of Francisella (Schu4, LVS, OR960246, U112) and identified distinct classes of differentially expressed genes during this process.

2015-05-02 | GSE68478 | GEO

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