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.

肺炎克雷伯菌序列类型 258 (Kp ST258) 是医疗保健相关肺炎的主要原因。然而，尽管它表达免疫刺激性脂多糖，可以激活快速的炎症反应和细菌清除，但仍不清楚它如何导致长期感染。我们预测宿主细胞中细菌引起的代谢应激会形成耐受感染的免疫反应。我们结合原位代谢成像和转录分析来证明 Kp ST258 激活宿主谷氨酰胺分解和脂肪酸氧化。这种反应创造了一个富含氧化剂的微环境，有利于抗炎骨髓细胞的积累。在这种情况下，代谢活跃的 Kp ST258 会引发抗病免疫反应。反过来，细菌通过上调 VI 型分泌系统来适应气道氧化剂，该系统在全球 ST258 菌株中高度保守。因此，Kp ST258 在医院环境中的全球成功很大程度上可以通过在宿主体内激发的代谢活动来促进疾病耐受性来解释。