Journal article
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
Infection and immunity, Vol.81(8), pp.2800-2811
08/2013
DOI: 10.1128/IAI.00073-13
PMCID: PMC3719569
PMID: 23716606
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.
Details
- Title: Subtitle
- 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
- Creators
- Matthew Faron - University of Iowa Graduate Program in Genetics, University of Iowa, Iowa City, Iowa, USAJoshua R FletcherJed A RasmussenMatthew E LongLee-Ann H AllenBradley D Jones
- Resource Type
- Journal article
- Publication Details
- Infection and immunity, Vol.81(8), pp.2800-2811
- DOI
- 10.1128/IAI.00073-13
- PMID
- 23716606
- PMCID
- PMC3719569
- ISSN
- 0019-9567
- eISSN
- 1098-5522
- Grant note
- T32 GM008629 / NIGMS NIH HHS I01 BX000513 / BLRD VA 2U54 AI057160 / NIAID NIH HHS P01 AI044642 / NIAID NIH HHS 2P01 AI044642 / NIAID NIH HHS U54 AI057160 / NIAID NIH HHS 5P01 AI044642-11 / NIAID NIH HHS
- Language
- English
- Date published
- 08/2013
- Academic Unit
- Microbiology and Immunology; Infectious Diseases; Internal Medicine
- Record Identifier
- 9984083281502771
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