title: Interplay between the QseC and QseE bacterial adrenergic sensor kinases in Salmonella enterica serovar Typhimurium pathogenesis.
abstract: The bacterial adrenergic sensor kinases QseC and QseE respond to epinephrine and/or norepinephrine to initiate a complex phosphorelay regulatory cascade that modulates virulence gene expression in several pathogens. We have previously shown that QseC activates virulence gene expression in Salmonella enterica serovar Typhimurium. Here we report the role of QseE in S. Typhimurium pathogenesis as well as the interplay between these two histidine sensor kinases in gene regulation. An S. Typhimurium qseE mutant is hampered in the invasion of epithelial cells and intramacrophage replication. The ΔqseC strain is highly attenuated for intramacrophage survival but has only a minor defect in invasion. However, the ΔqseEC strain has only a slight attenuation in invasion, mirroring the ΔqseC strain, and has an intermediary intramacrophage replication defect in comparison to the ΔqseE and ΔqseC strains. The expressions of the sipA and sopB genes, involved in the invasion of epithelial cells, are activated by epinephrine via QseE. The expression levels of these genes are still decreased in the ΔqseEC double mutant, albeit to a lesser extent, congruent with the invasion phenotype of this mutant. The expression level of the sifA gene, important for intramacrophage replication, is decreased in the qseE mutant and the ΔqseEC double mutant grown in vitro. However, as previously reported by us, the epinephrine-dependent activation of this gene occurs via QseC. In the systemic model of S. Typhimurium infection of BALB/c mice, the qseC and qseE mutants are highly attenuated, while the double mutant has an intermediary phenotype. Altogether, these data suggest that both adrenergic sensors play an important role in modulating several aspects of S. Typhimurium pathogenesis.
authors.affiliation: Department of Microbiology, The University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Cristiano G
authors.initials: CG
authors.lastname: Moreira
authors.forename: Vanessa
authors.initials: V
authors.lastname: Sperandio
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004837:Epinephrine / Q000494:pharmacology; D004847:Epithelial Cells / Q000382:microbiology; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D006367:HeLa Cells; D000071677:Histidine Kinase; D006801:Humans; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D012481:Salmonella Infections, Animal / Q000382:microbiology / Q000401:mortality; D012486:Salmonella typhimurium / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D011494:Protein Kinases; D000071677:Histidine Kinase; D004837:Epinephrine