Antibiotic therapy and host cells frequently fail to eliminate invasive bacterial pathogens due to the emergence of antibiotic resistance, resulting in the relapse and recurrence of infections. Bacteria evolve various strategies to persist and survive in epithelial cells, a front‐line barrier of host tissues counteracting invasion; however, it remains unclear how bacteria hijack cellular responses to promote cytoplasmic survival under antibiotic therapy. Here, it is demonstrated that extracellular bacteria show invasive behavior and survive in epithelial cells in both in vivo and in vitro models, to increase antibiotic tolerance. In turn, sublethal levels of antibiotics increase bacterial invasion through promoting the production of bacterial virulence factors. Furthermore, antibiotic treatments interrupt lysosomal acidification in autophagy due to the internalized bacteria, using Bacillus cereus and ciprofloxacin as a model. In addition, it is found that sublethal levels of ciprofloxacin cause mitochondrial dysfunction and reactive oxygen species (ROS) accumulation to impair lysosomal vascular tape ATPase (V‐ATPase) to further promote bacterial persistence. Collectively, these results highlight the potential of host cells mediated antibiotic tolerance, which markedly compromises antibiotic efficacy and worsens the outcomes of infection.

中文翻译：

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亚致死水平的抗生素促进上皮细胞中细菌的持久性。

由于出现抗生素抗性，抗生素治疗和宿主细胞经常无法消除侵入性细菌病原体，从而导致感染的复发和复发。细菌进化出各种策略以在上皮细胞中维持和生存，而上皮细胞是宿主组织抵抗入侵的一线屏障。然而，尚不清楚细菌如何在抗生素治疗下劫持细胞反应以促进细胞质存活。在此，证明了胞外细菌在体内和体外模型中均表现出侵袭性行为并在上皮细胞中存活，以增加抗生素耐受性。反之，亚致死水平的抗生素通过促进细菌毒力因子的产生而增加细菌的入侵。此外，蜡状芽孢杆菌和环丙沙星为模型。此外，发现环丙沙星的亚致死水平会导致线粒体功能障碍和活性氧（ROS）积累，从而削弱溶酶体血管带ATPase（V-ATPase），从而进一步促进细菌的持久性。总的来说，这些结果突出了宿主细胞介导的抗生素耐受性的潜力，这显着损害了抗生素功效并恶化了感染的结果。