MglA regulates Francisella tularensis subsp novicida (Francisella novicida) response to starvation and oxidative stress

MgIA 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 MgIA. The differences in relative protein amounts between wild-type F. novicida and the mgl4 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 mgl4 mutant were homologs of oxidative and general stress response proteins. The F. novicida mgl4 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 mgl4 mutant also showed increased survival upon exposure to hydrogen peroxide, likely due to increased amounts of the catalase KatG. Our results suggested that MgIA coordinates the stress response of F. tularensis and is likely essential for bacterial survival in harsh environments.