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在原发性阿米巴脑膜脑炎的小鼠模型中,分离株的毒力差异显著。

Virulence of isolates varies significantly in the mouse model of primary amoebic meningoencephalitis.

作者信息

Russell A Cassiopeia, Schiff Erica, Dainis Joseph, Jones Håkon, Rice Christopher A, Kyle Dennis E

机构信息

University of Georgia, Athens, Georgia, USA.

出版信息

bioRxiv. 2025 May 20:2025.05.20.655168. doi: 10.1101/2025.05.20.655168.

Abstract

is a small free-living amoeba that causes an acute, fatal disease called primary amoebic meningoencephalitis (PAM). One persisting question is why few people succumb to disease when so many are potentially exposed. We tested the hypothesis that isolates vary in virulence and in the minimum infectious dose required to induce disease by using a mouse model of PAM and intranasally inoculating dilutions of five clinical isolates of . Results showed significant differences in onset of severe disease and mortality rates between isolates. Remarkably, for isolate V596, 100 amoebae produced 100% mortality within 5 days. In contrast, higher numbers of amoebae were required for other isolates and mice survived for >2 weeks. Concurrently, we developed an virulence assay by comparing feeding rates between amoebae isolates seeded onto Vero cells. We observed a positive correlation between cytopathic effects and virulence .

摘要

是一种小型自由生活的变形虫,可引发一种名为原发性阿米巴脑膜脑炎(PAM)的急性致命疾病。一个一直存在的问题是,为何在众多可能接触到病原体的人中,只有少数人会患病。我们通过使用PAM小鼠模型并经鼻接种五种临床分离株的稀释液,来检验分离株在毒力以及引发疾病所需的最小感染剂量方面存在差异这一假设。结果显示,各分离株在严重疾病的发病时间和死亡率上存在显著差异。值得注意的是,对于分离株V596,100个变形虫在5天内导致了100%的死亡率。相比之下,其他分离株则需要更多数量的变形虫,并且小鼠存活时间超过2周。同时,我们通过比较接种在Vero细胞上的变形虫分离株之间的摄食率,开发了一种变形虫毒力测定方法。我们观察到细胞病变效应与毒力之间存在正相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c289/12139919/9c724794f920/nihpp-2025.05.20.655168v1-f0001.jpg

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