Host Stress Signals Stimulate Pneumococcal Transition from Colonization to Dissemination into the Lungs.
Host Stress Signals Stimulate Pneumococcal Transition from Colonization to Dissemination into the Lungs.
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DOI：
10.1128/mbio.02569-21
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发表时间：
2021-12-21
期刊：
影响因子：
6.4
通讯作者：
Yesilkaya H
中科院分区：
文献类型：
--
作者：
Alghofaili F;Najmuldeen H;Kareem BO;Shlla B;Fernandes VE;Danielsen M;Ketley JM;Freestone P;Yesilkaya H
肺炎链球菌是鼻咽部的无症状定植者，但它也是人类最重要的细菌病原体之一，引起广泛的轻度至危及生命的疾病。肺炎球菌从寄生性生活方式转变为寄生性生活方式的基础尚不完全清楚。我们推测，暴露于主机的儿茶酚胺应激激素是重要的这种过渡。在这项研究中，我们证明，肺炎球菌预先暴露于应激过程中释放的一种激素，去甲肾上腺素（NE），与未经治疗的肺炎球菌相比，其从鼻咽转移到肺部的能力增加。NE治疗的肺炎球菌的检查发现代谢谱，细胞协会，胶囊合成和细胞大小的重大改变。通过系统突变所有12个双组分和1个孤儿调节系统，我们还确定了一个独特的基因调控回路，参与肺炎球菌识别和对人类应激激素的反应。
Streptococcus pneumoniae is an asymptomatic colonizer of the nasopharynx, but it is also one of the most important bacterial pathogens of humans, causing a wide range of mild to life-threatening diseases. The basis of the pneumococcal transition from a commensal to a parasitic lifestyle is not fully understood. We hypothesize that exposure to host catecholamine stress hormones is important for this transition. In this study, we demonstrated that pneumococci preexposed to a hormone released during stress, norepinephrine (NE), have an increased capacity to translocate from the nasopharynx into the lungs compared to untreated pneumococci. Examination of NE-treated pneumococci revealed major alterations in metabolic profiles, cell associations, capsule synthesis, and cell size. By systemically mutating all 12 two-component and 1 orphan regulatory systems, we also identified a unique genetic regulatory circuit involved in pneumococcal recognition and responsiveness to human stress hormones.