小柯机器人

美国哥伦比亚大学的Alice Prince和Tania Wong Fok Lung团队合作发现肺炎克雷伯菌诱导宿主代谢应激，促进对肺部感染的耐受性。2022年4月11日出版的《细胞—代谢》杂志发表了这一研究成果。

他们预测，宿主细胞中的细菌引起的代谢应激形成了一种免疫反应，可以耐受感染。他们结合原位代谢成像和转录分析，证明肺炎克雷伯菌序列258型（Kp ST258）激活宿主谷氨酸解氨和脂肪酸氧化。这种反应创造了一个富含氧化剂的微环境，有利于抗炎性髓样细胞的积聚。在这种情况下，具有代谢活性的Kp ST258会引发一种疾病耐受性免疫反应。反过来，细菌通过上调VI型分泌系统来适应气道氧化剂，该系统在世界各地的ST258菌株中高度保守。因此，Kp ST258在医院环境中的整体成功，在很大程度上可以用宿主体内激发的促进疾病耐受的代谢活动来解释。

据悉，Kp ST258是医疗相关肺炎的主要病因。然而，尽管它表达免疫刺激性脂多糖，但仍不清楚它是如何导致长期感染的，脂多糖应能激活快速的炎症反应和细菌清除。

附：英文原文

Title: Klebsiella pneumoniae induces host metabolic stress that promotes tolerance to pulmonary infection

Author: Tania Wong Fok Lung, Daniel Charytonowicz, Kristin G. Beaumont, Shivang S. Shah, Shwetha H. Sridhar, Claire L. Gorrie, Andre Mu, Casey E. Hofstaedter, David Varisco, Thomas H. McConville, Marija Drikic, Brandon Fowler, Andreacarola Urso, Wei Shi, Dario Fucich, Medini K. Annavajhala, Ibrahim N. Khan, Irina Oussenko, Nancy Francoeur, Melissa L. Smith, Brent R. Stockwell, Ian A. Lewis, Abderrahman Hachani, Swikrity Upadhyay Baskota, Anne-Catrin Uhlemann, Danielle Ahn, Robert K. Ernst, Benjamin P. Howden, Robert Sebra, Alice Prince

Issue&Volume: 2022-04-11

Abstract: K. pneumoniae sequence type 258 (Kp ST258) is a major cause of healthcare-associated pneumonia. However, it remains unclear how it causes protracted courses of infection in spite of its expression of immunostimulatory lipopolysaccharide, which should activate a brisk inflammatory response and bacterial clearance. We predicted that the metabolic stress induced by the bacteria in the host cells shapes an immune response that tolerates infection. We combined in situ metabolic imaging and transcriptional analyses to demonstrate that Kp ST258 activates host glutaminolysis and fatty acid oxidation. This response creates an oxidant-rich microenvironment conducive to the accumulation of anti-inflammatory myeloid cells. In this setting, metabolically active Kp ST258 elicits a disease-tolerant immune response. The bacteria, in turn, adapt to airway oxidants by upregulating the type VI secretion system, which is highly conserved across ST258 strains worldwide. Thus, much of the global success of Kp ST258 in hospital settings can be explained by the metabolic activity provoked in the host that promotes disease tolerance.

DOI: 10.1016/j.cmet.2022.03.009

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00097-3

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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