ArticleInfection and immunity2013
The Francisella tularensis migR, trmE, and cphA genes contribute to F. tularensis pathogenicity island gene regulation and intracellular growth by modulation of the stress alarmone ppGpp.
Article in Infection and immunity, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 22 citations in OpenAlex.
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- Stringent Starvation Protein Regulates Prodiginine Biosynthesis via Affecting Siderophore Production inApplied and environmental microbiology · 2021Article
- Control ofMicroorganisms · 2020Review
- Stringent response governs the oxidative stress resistance and virulence of Francisella tularensis.PloS one · 2019Article
- Whole genome transcriptomics reveals global effects including up-regulation of Francisella pathogenicity island gene expression during active stringent response in the highly virulent Francisella tularensis subsp. tularensis SCHU S4.Microbiology (Reading, England) · 2017Article
- Dissection of the molecular circuitry controlling virulence inGenes & development · 2017Article
- Differential Growth ofFrontiers in microbiology · 2017Article
- Perspectives and Insights into the Competition for Aminoacyl-tRNAs between the Translational Machinery and for tRNA Dependent Non-Ribosomal Peptide Bond Formation.Life (Basel, Switzerland) · 2015Review
- Interactions of Francisella tularensis with Alveolar Type II Epithelial Cells and the Murine Respiratory Epithelium.PloS one · 2015Article
- Role of (p)ppGpp in Viability and Biofilm Formation of Actinobacillus pleuropneumoniae S8.PloS one · 2015Article
- tRNA modification enzymes GidA and MnmE: potential role in virulence of bacterial pathogens.International journal of molecular sciences · 2014Review
- Coordinate control of virulence gene expression in Francisella tularensis involves direct interaction between key regulators.Journal of bacteriology · 2014Article
- Uncovering the components of the Francisella tularensis virulence stealth strategy.Frontiers in cellular and infection microbiology · 2014Review
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- Differential Rickettsial Transcription in Bloodfeeding and Non-Bloodfeeding Arthropod Hosts.PloS oneArticle
- Characterization of Francisella species isolated from the cooling water of an air conditioning system.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology]Article
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Authors and funding
6 authors at 2 institutions in 1 country.
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Abstract
The Francisella tularensis pathogenicity island (FPI) encodes many proteins that are required for virulence. Expression of these genes depends upon the FevR (PigR) regulator and its interactions with the MglA/SspA and RNA polymerase transcriptional complex. Experiments to identify how transcription of the FPI genes is activated have led to identification of mutations within the migR, trmE, and cphA genes that decrease FPI expression. Recent data demonstrated that the small alarmone ppGpp, produced by RelA and SpoT, is important for stabilizing MglA/SspA and FevR (PigR) interactions in Francisella. Production of ppGpp is commonly known to be activated by cellular and nutritional stress in bacteria, which indicates that cellular and nutritional stresses act as important signals for FPI activation. In this work, we demonstrate that mutations in migR, trmE, or cphA significantly reduce ppGpp accumulation. The reduction in ppGpp levels was similar for each of the mutants and correlated with a corresponding reduction in iglA reporter expression. In addition, we observed that there were differences in the ability of each of these mutants to replicate within various mammalian cells, indicating that the migR, trmE, and cphA genes are likely parts of different cellular stress response pathways in Francisella. These results also indicate that different nutritional and cellular stresses exist in different mammalian cells. This work provides new information to help understand how Francisella regulates its virulence genes in response to host cell environments, and it contributes to our growing knowledge of this highly successful bacterial pathogen.
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