title: Elucidation of a mechanism of oxidative stress regulation in Francisella tularensis live vaccine strain.
abstract: 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.
authors.affiliation: Department of Basic and Social Sciences, Albany College of Pharmacy and Health Sciences, Albany, NY, USA.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Basic and Social Sciences, Albany College of Pharmacy and Health Sciences, Albany, NY, USA.
authors.forename: Vincenzo C
authors.initials: VC
authors.lastname: Russo
authors.affiliation: Department of Microbiology and Immunology, New York Medical College, Valhalla, NY, USA.
authors.forename: Seham M
authors.initials: SM
authors.lastname: Rabadi
authors.affiliation: Department of Pathology, Westchester Medical Center, Valhalla, NY, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Jen
authors.affiliation: Department of Basic and Social Sciences, Albany College of Pharmacy and Health Sciences, Albany, NY, USA.
authors.forename: Sally V
authors.initials: SV
authors.lastname: Catlett
authors.affiliation: Department of Microbiology and Immunology, New York Medical College, Valhalla, NY, USA.
authors.forename: Chandra Shekhar
authors.initials: CS
authors.lastname: Bakshi
authors.affiliation: Department of Basic and Social Sciences, Albany College of Pharmacy and Health Sciences, Albany, NY, USA.
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Malik
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D001428:Bacterial Vaccines / Q000276:immunology; D005604:Francisella tularensis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D017353:Gene Deletion; D006801:Humans; D051379:Mice; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology*; D040901:Proteomics / Q000379:methods; D017382:Reactive Oxygen Species / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D014406:Tularemia / Q000382:microbiology / Q000517:prevention & control*; D014613:Vaccines, Attenuated / Q000276:immunology; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D000975:Antioxidants; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D017382:Reactive Oxygen Species; D012097:Repressor Proteins; D014613:Vaccines, Attenuated; D037521:Virulence Factors