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Elucidation of a mechanism of oxidative stress regulation in Francisella tularensis live vaccine strain
Author(s) -
Ma Zhuo,
Russo Vincenzo C.,
Rabadi Seham M.,
Jen Yu,
Catlett Sally V.,
Bakshi Chandra Shekhar,
Malik Meenakshi
Publication year - 2016
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.13426
Subject(s) - francisella tularensis , biology , tularemia , francisella , virulence , microbiology and biotechnology , oxidative stress , regulon , intracellular , regulation of gene expression , gene , genetics , biochemistry
Summary Francisella tularensis causes a lethal human disease known as tularemia. As an intracellular pathogen, Francisella survives and replicates in phagocytic cells, such as macrophages. However, to establish an intracellular niche, Francisella must overcome the oxidative stress posed by the reactive oxygen species (ROS) produced by the infected macrophages. OxyR and SoxR/S are two well‐characterized transcriptional regulators of oxidative stress responses in several bacterial pathogens. Only the OxyR homolog is present in F. tularensis , while the SoxR homologs are absent. The functional role of OxyR has not been established in F. tularensis . We demonstrate that OxyR regulates oxidative stress responses and provides resistance against ROS, thereby contributing to the survival of the F. tularensis subsp. holarctica live vaccine strain (LVS) in macrophages and epithelial cells and contributing to virulence in mice. Proteomic analysis reveals the differential production of 128 proteins in the oxyR gene deletion mutant, indicating its global regulatory role in the oxidative stress response of F. tularensis . Moreover, OxyR regulates the transcription of the primary antioxidant enzyme genes by binding directly to their putative promoter regions. This study demonstrates that OxyR is an important virulence factor and transcriptional regulator of the oxidative stress response of the F. tularensis LVS.