Institute for Cell and Molecular , The Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, United Kingdom.
J Bacteriol. 2010 Feb;192(3):714-24. doi: 10.1128/JB.01329-09. Epub 2009 Nov 20.
Bacterial sensing of environmental signals plays a key role in regulating virulence and mediating bacterium-host interactions. The sensing of the neuroendocrine stress hormones epinephrine (adrenaline) and norepinephrine (noradrenaline) plays an important role in modulating bacterial virulence. We used MudJ transposon mutagenesis to globally screen for genes regulated by neuroendocrine stress hormones in Salmonella enterica serovar Typhimurium. We identified eight hormone-regulated genes, including yhaK, iroC, nrdF, accC, yedP, STM3081, and the virulence-related genes virK and mig14. The mammalian alpha-adrenergic receptor antagonist phentolamine reversed the hormone-mediated effects on yhaK, virK, and mig14 but did not affect the other genes. The beta-adrenergic receptor antagonist propranolol had no activity in these assays. The virK and mig14 genes are involved in antimicrobial peptide resistance, and phenotypic screens revealed that exposure to neuroendocrine hormones increased the sensitivity of S. Typhimurium to the antimicrobial peptide LL-37. A virK mutant and a virK mig14 double mutant also displayed increased sensitivity to LL-37. In contrast to enterohemorrhagic Escherichia coli (EHEC), we have found no role for the two-component systems QseBC and QseEF in the adrenergic regulation of any of the identified genes. Furthermore, hormone-regulated gene expression could not be blocked by the QseC inhibitor LED209, suggesting that sensing of hormones is mediated through alternative signaling pathways in S. Typhimurium. This study has identified a role for host-derived neuroendocrine stress hormones in downregulating S. Typhimurium virulence gene expression to the benefit of the host, thus providing further insights into the field of host-pathogen communication.
细菌对环境信号的感应在调节毒力和介导细菌与宿主相互作用方面起着关键作用。神经内分泌应激激素肾上腺素（肾上腺素）和去甲肾上腺素（去甲肾上腺素）的感应在调节细菌毒力方面起着重要作用。我们使用 MudJ 转座子诱变剂全局筛选沙门氏菌血清型鼠伤寒菌中受神经内分泌应激激素调节的基因。我们确定了 8 个受激素调节的基因，包括 yhaK、iroC、nrdF、accC、yedP、STM3081 以及与毒力相关的基因 virK 和 mig14。哺乳动物的α-肾上腺素能受体拮抗剂苯肾上腺素逆转了激素对 yhaK、virK 和 mig14 的影响，但对其他基因没有影响。β-肾上腺素能受体拮抗剂普萘洛尔在这些测定中没有活性。virK 和 mig14 基因参与抗菌肽耐药性，表型筛选显示，暴露于神经内分泌激素会增加鼠伤寒菌对抗菌肽 LL-37 的敏感性。virK 突变体和 virK mig14 双突变体对 LL-37 的敏感性也增加。与肠出血性大肠杆菌（EHEC）不同，我们没有发现双组分系统 QseBC 和 QseEF 在肾上腺素调节任何鉴定基因中的作用。此外，激素调节的基因表达不能被 QseC 抑制剂 LED209 阻断，这表明激素的感应是通过沙门氏菌中的替代信号通路介导的。这项研究确定了宿主来源的神经内分泌应激激素在下调鼠伤寒菌毒力基因表达方面的作用，有利于宿主，从而为宿主-病原体通讯领域提供了进一步的见解。
