Department of Microbiology, The University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Infect Immun. 2012 Dec;80(12):4344-53. doi: 10.1128/IAI.00803-12. Epub 2012 Oct 1.
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.
细菌肾上腺素传感器激酶 QseC 和 QseE 响应肾上腺素和/或去甲肾上腺素，启动复杂的磷酸传递级联反应，调节几种病原体的毒力基因表达。我们之前已经表明，QseC 激活鼠伤寒沙门氏菌 Typhimurium 的毒力基因表达。在这里，我们报告了 QseE 在鼠伤寒沙门氏菌发病机制中的作用，以及这两种组氨酸传感器激酶在基因调控中的相互作用。鼠伤寒沙门氏菌 qseE 突变体在侵袭上皮细胞和巨噬细胞内复制方面受到阻碍。ΔqseC 菌株在巨噬细胞内生存能力高度衰减，但侵袭缺陷较小。然而，ΔqseEC 菌株的侵袭衰减程度仅略有下降，与 ΔqseC 菌株相似，与 ΔqseE 和 ΔqseC 菌株相比，其巨噬细胞内复制缺陷处于中间水平。参与上皮细胞侵袭的 sipA 和 sopB 基因的表达通过 QseE 被肾上腺素激活。这些基因的表达水平在 ΔqseEC 双突变体中仍然降低，尽管程度较小，与该突变体的侵袭表型一致。对于巨噬细胞内复制很重要的 sifA 基因的表达水平在 qseE 突变体和体外生长的 ΔqseEC 双突变体中降低。然而，正如我们之前报道的，该基因的肾上腺素依赖性激活是通过 QseC 发生的。在 BALB/c 小鼠鼠伤寒沙门氏菌感染的系统模型中，qseC 和 qseE 突变体高度衰减，而双突变体具有中间表型。总的来说，这些数据表明，两种肾上腺素传感器在调节鼠伤寒沙门氏菌发病机制的几个方面都发挥着重要作用。
