MglA Regulates Transcription of Virulence Factors Necessary for Francisella tularensis Intraamoebae and Intramacrophage Survival

Francisella tularensis is able to survive and grow within macrophages, a trait that contributes to pathogenesis. Several genes have been identified that are important for intramacrophage survival, including mglA and iglC. F. tularensis is also able to survive within amoebae. It is shown here that F....

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2004-03, Vol.101 (12), p.4246-4249
Main Authors: Lauriano, Crystal M., Barker, Jeffrey R., Yoon, Sang-Sun, Nano, Francis E., Arulanandam, Bernard P., Hassett, Daniel J., Klose, Karl E., Falkow, Stanley
Format: Article
Language:English
Subjects:
Amoeba - microbiology
Animals
Bacteria
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Biological Sciences
Female
Francisella
Francisella tularensis
Francisella tularensis - genetics
Francisella tularensis - metabolism
Francisella tularensis - pathogenicity
Gene Expression Regulation
Genes
Host-Parasite Interactions
Infections
Lethal dose 50
Macrophages
Macrophages - microbiology
Mice
Microbiology
Mutation
Reverse transcriptase polymerase chain reaction
RNA
Transcriptional regulatory elements
Virulence
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Summary:Francisella tularensis is able to survive and grow within macrophages, a trait that contributes to pathogenesis. Several genes have been identified that are important for intramacrophage survival, including mglA and iglC. F. tularensis is also able to survive within amoebae. It is shown here that F. tularensis mglA and iglC mutant strains are not only defective for survival and replication within the macrophage-like cell line J774, but also within Acanthamoebae castellanii. Moreover, these strains are highly attenuated for virulence in mice, suggesting that a common mechanism underlies intramacrophage and intraamoebae survival and virulence. A 2D gel analysis of cell extracts of wild-type and mglA mutant strains revealed that at least seven prominent proteins were at low levels in the mglA mutant, and one MglA-regulated protein was identified as the IglC protein. RT-PCR analysis demonstrated reduced transcription of iglC and several other known and suspected virulence genes in the mglA mutant. Thus, MglA regulates the transcription of virulence factors of F. tularensis that contribute to intramacrophage and intraamoebae survival.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0307690101