Clinical studies report that viral infections promote acute or chronic bacterial infections at multiple host sites. These viral-bacterial co-infections are widely linked to more severe clinical outcomes. In experimental models in vitro and in vivo, virus-induced interferon responses can augment host susceptibility to secondary bacterial infection. Here, we used a cell-based screen to assess 389 interferon-stimulated genes (ISGs) for their ability to induce chronic Pseudomonas aeruginosa infection. We identified and validated five ISGs that were sufficient to promote bacterial infection. Furthermore, we dissected the mechanism of action of hexokinase 2 (HK2), a gene involved in the induction of aerobic glycolysis, commonly known as the Warburg effect. We report that HK2 upregulation mediates the induction of Warburg effect and secretion of L-lactate, which enhances chronic P. aeruginosa infection. These findings elucidate how the antiviral immune response renders the host susceptible to secondary bacterial infection, revealing potential strategies for viral-bacterial co-infection treatment.

中文翻译：

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干扰素信号驱动上皮代谢重编程以促进继发性细菌感染。

临床研究报告称，病毒感染会促进多个宿主部位的急性或慢性细菌感染。这些病毒-细菌混合感染与更严重的临床结果广泛相关。在体外和体内实验模型中，病毒诱导的干扰素反应可以增加宿主对继发细菌感染的易感性。在这里，我们使用基于细胞的筛选来评估 389 个干扰素刺激基因 (ISG) 诱导慢性铜绿假单胞菌感染的能力。我们确定并验证了五种足以促进细菌感染的 ISG。此外，我们剖析了己糖激酶 2 (HK2) 的作用机制，该基因参与诱导有氧糖酵解，通常称为 Warburg 效应。我们报道 HK2 上调介导 Warburg 效应的诱导和 L-乳酸的分泌，从而增强慢性铜绿假单胞菌感染。这些发现阐明了抗病毒免疫反应如何使宿主容易受到继发细菌感染，揭示了病毒-细菌合并感染治疗的潜在策略。