棘阿米巴原蟲（Acanthamoeba castellanii）有伺機感染人類角膜的致病能力，在感染後宿主可能出現嚴重的角膜炎症狀，甚至需要進行眼球摘除手術。棘阿米巴原蟲角膜炎的流行率低，但過去研究發現人類經常暴露於與棘阿米巴原蟲接觸的風險，且目前對於棘阿米巴原蟲的致病機制尚有許多未知。棘阿米巴原蟲是自由營生的原生生物，廣泛存在於各類土壤及水體環境中，以多樣的微生物為食。近來研究發現，部分棘阿米巴致病因子與其捕食微生物的機制類似，棘阿米巴表面受器辨識宿主或獵物後，啟動下游吞噬作用反應。實驗室中所使用的棘阿米巴蟲株可能因長期以液態培養基培養，造成辨識固態食物來源或吞噬作用的弱化，進而導致致病機制難以釐清。本研究中，我們重新馴化棘阿米巴原蟲，使其可以在低營養培養基中以細菌為食，並發現其毒性相關表現增強。透過代謝體和基因體學技術，我們比較兩者後發現棘阿米巴在改以細菌為食後，四種胺基酸的代謝途徑被調控，包含支鏈胺基酸的分解與生合成；此外，胞吞作用、吞噬體、和自噬作用途徑中大部分基因表現量上調，這些途徑影響了棘阿米巴原蟲適應低營養環境和捕食能力。除了棘阿米巴本身的變化之外，原蟲也會造成周邊細菌的表現型變化，進而影響其毒性，並間接影響宿主健康。在與施氏假性單胞菌的共培養實驗中，發現棘阿米巴原蟲會造成其移動能力下降，而以細菌為食的棘阿米巴則可造成此細菌表現型變化更為穩定。本研究提供了棘阿米巴共培養與感染模型的新方向，並增進對棘阿米巴毒性更深入的了解。

Acanthamoeba castellanii, a free-living protozoan, possesses opportunistic pathogenicity for human corneas, potentially inducing severe keratitis symptoms and even necessitating enucleation surgery following infection. While the prevalence of Acanthamoeba keratitis is low, studies have shown frequent human exposure to Acanthamoeba, highlighting the need for a deeper understanding of its pathogenic mechanisms. In this study, we reconditioned A. castellanii to thrive in a low-nutrient culture medium and feed on heat-killed bacteria. Interestingly, this adaptation led to an enhancement of its virulence-related gene expressions. Through metabolomic and genomic analyses, we observed regulatory changes in four amino acid metabolic pathways, including the degradation and biosynthesis of branched-chain amino acids. Additionally, genes associated with phagocytosis, phagosomes, and autophagy pathways were predominantly upregulated, influencing Acanthamoeba's adaptation to low-nutrient environments and its predatory capabilities. Beyond the changes in Acanthamoeba itself, the protozoan induces phenotypic alterations in surrounding bacteria, impacting their virulence and indirectly affecting host health. Our co-incubation experiments with Pseudomonas stutzeri revealed that A. castellanii caused a reduction in bacterial motility, and amoebae preying on bacteria-induced more stable phenotypic changes in the bacteria. Based on our findings, we concluded that the virulence of A. castellanii and protozoan-bacterial interaction were largely affected by the composition of the co-culture environments. Additionally, this study introduces novel directions for A. castellanii co-culturing and infection models, advancing our understanding of A. castellanii virulence.

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