title: A Redox-Responsive Transcription Factor Is Critical for Pathogenesis and Aerobic Growth of Listeria monocytogenes.
abstract: Bacterial pathogens have evolved sophisticated mechanisms to sense and adapt to redox stress in nature and within the host. However, deciphering the redox environment encountered by intracellular pathogens in the mammalian cytosol is challenging, and that environment remains poorly understood. In this study, we assessed the contributions of the two redox-responsive, Spx-family transcriptional regulators to the virulence ofListeria monocytogenes, a Gram-positive facultative intracellular pathogen. Spx-family proteins are highly conserved inFirmicutes, and theL. monocytogenesgenome contains two paralogues,spxA1andspxA2Here, we demonstrate thatspxA1, but notspxA2, is required for the oxidative stress response and pathogenesis. SpxA1 function appeared to be conserved with theBacillus subtilishomologue, and resistance to oxidative stress required the canonical CXXC redox-sensing motif. Remarkably,spxA1was essential for aerobic growth, demonstrating thatL. monocytogenesSpxA1 likely regulates a distinct set of genes. Although the ΔspxA1mutant did not grow in the presence of oxygen in the laboratory, it was able to replicate in macrophages and colonize the spleens, but not the livers, of infected mice. These data suggest that the redox state of bacteria during infection differs significantly from that of bacteria growingin vitroFurther, the host cell cytosol may resemble an anaerobic environment, with tissue-specific variations in redox stress and oxygen concentration.
authors.affiliation: Graduate Group in Infectious Diseases and Immunity, School of Public Health, University of California, Berkeley, Berkeley, California, USA.
authors.forename: Aaron T
authors.initials: AT
authors.lastname: Whiteley
authors.affiliation: Department of Microbiology, University of Washington, Seattle, Washington, USA.
authors.forename: Brittany R
authors.initials: BR
authors.lastname: Ruhland
authors.affiliation: Department of Microbiology, University of Washington, Seattle, Washington, USA.
authors.forename: Mauna B
authors.initials: MB
authors.lastname: Edrozo
authors.affiliation: Department of Microbiology, University of Washington, Seattle, Washington, USA reniere@uw.edu.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Reniere
mesh_terms: D000332:Aerobiosis; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D008089:Listeria monocytogenes / Q000254:growth & development* / Q000472:pathogenicity*; D008088:Listeriosis / Q000382:microbiology / Q000473:pathology; D008099:Liver / Q000382:microbiology; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D013154:Spleen / Q000382:microbiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014774:Virulence
chemical_list: D014157:Transcription Factors
keywords: intracellular bacteria; pathogenesis; redox signaling; virulence regulation