title: MglA regulates Francisella tularensis subsp. novicida (Francisella novicida) response to starvation and oxidative stress.
abstract: MglA is a transcriptional regulator of genes that contribute to the virulence of Francisella tularensis, a highly infectious pathogen and the causative agent of tularemia. This study used a label-free shotgun proteomics method to determine the F. tularensis subsp. novicida (F. novicida) proteins that are regulated by MglA. The differences in relative protein amounts between wild-type F. novicida and the mglA mutant were derived directly from the average peptide precursor ion intensity values measured with the mass spectrometer by using a suite of mathematical algorithms. Among the proteins whose relative amounts changed in an F. novicida mglA mutant were homologs of oxidative and general stress response proteins. The F. novicida mglA mutant exhibited decreased survival during stationary-phase growth and increased susceptibility to killing by superoxide generated by the redox-cycling agent paraquat. The F. novicida mglA mutant also showed increased survival upon exposure to hydrogen peroxide, likely due to increased amounts of the catalase KatG. Our results suggested that MglA coordinates the stress response of F. tularensis and is likely essential for bacterial survival in harsh environments.
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, University of Washington, Seattle, WA, USA. tguina@u.washington.edu
authors.forename: Tina
authors.initials: T
authors.lastname: Guina
authors.forename: Dragan
authors.initials: D
authors.lastname: Radulovic
authors.forename: Arya J
authors.initials: AJ
authors.lastname: Bahrami
authors.forename: Diana L
authors.initials: DL
authors.lastname: Bolton
authors.forename: Laurence
authors.initials: L
authors.lastname: Rohmer
authors.forename: Kendan A
authors.initials: KA
authors.lastname: Jones-Isaac
authors.forename: Jinzy
authors.initials: J
authors.lastname: Chen
authors.forename: Larry A
authors.initials: LA
authors.lastname: Gallagher
authors.forename: Byron
authors.initials: B
authors.lastname: Gallis
authors.forename: Soyoung
authors.initials: S
authors.lastname: Ryu
authors.forename: Greg K
authors.initials: GK
authors.lastname: Taylor
authors.forename: Mitchell J
authors.initials: MJ
authors.lastname: Brittnacher
authors.forename: Colin
authors.initials: C
authors.lastname: Manoil
authors.forename: David R
authors.initials: DR
authors.lastname: Goodlett
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D005604:Francisella tularensis / Q000235:genetics / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity* / Q000502:physiology*; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D018869:Heat-Shock Response; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D018384:Oxidative Stress; D040901:Proteomics; D013047:Specific Pathogen-Free Organisms; D014406:Tularemia / Q000382:microbiology; D014774:Virulence
chemical_list: D001426:Bacterial Proteins