PDF(Pubmed)
Abstract：
Bacterivorous protists are thought to serve as training grounds for bacterial pathogens by subjecting them to the same hostile conditions that they will encounter in the human host. Bacteria that survive intracellular digestion exhibit enhanced virulence and stress resistance after successful passage through protozoa but the underlying mechanisms are unknown. Here we show that the opportunistic pathogen Burkholderia cenocepacia survives phagocytosis by ciliates found in domestic and hospital sink drains, and viable bacteria are expelled packaged in respirable membrane vesicles with enhanced resistance to oxidative stress, desiccation, and antibiotics, thereby contributing to pathogen dissemination in the environment. Reactive oxygen species generated within the protozoan phagosome promote the formation of persisters tolerant to ciprofloxacin by activating the bacterial SOS response. In addition, we show that genes encoding antioxidant enzymes are upregulated during passage through ciliates increasing bacterial resistance to oxidative radicals. We prove that suppression of the SOS response impairs bacterial intracellular survival and persister formation within protists. This study highlights the significance of protozoan food vacuoles as niches that foster bacterial adaptation in natural and built environments and suggests that persister switch within phagosomes may be a widespread phenomenon in bacteria surviving intracellular digestion.
摘要：
细菌原生生物被认为是细菌病原体的训练场，使它们经受与在人类宿主中遇到的相同的敌对条件。在细胞内消化中存活的细菌在成功通过原生动物后表现出增强的毒力和胁迫抗性，但潜在的机制尚不清楚。在这里，我们表明机会性病原体伯克霍尔德氏菌在家庭和医院水槽排水沟中发现的纤毛虫的吞噬作用中存活下来，活的细菌被排出包装在可吸入的膜囊泡中，具有增强的抗氧化应激能力，干燥和抗生素，从而有助于病原体在环境中的传播。原生动物吞噬体内产生的活性氧通过激活细菌SOS反应来促进对环丙沙星耐受的持久性物质的形成。此外,我们表明，编码抗氧化酶的基因在通过纤毛虫过程中上调，增加了细菌对氧化自由基的抵抗力。我们证明SOS反应的抑制会损害细菌的细胞内存活和原生生物内的持久形成。这项研究强调了原生动物食物液泡作为促进细菌在自然和建筑环境中适应的生态位的重要性，并表明吞噬体内的持能开关可能是细菌在细胞内消化中存活的普遍现象。
