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Abstract：
We previously observed a substantial burden of cryptococcal meningitis in Vietnam atypically arising in individuals who are uninfected with human immunodeficiency virus (HIV). This disease was associated with a single genotype of Cryptococcus neoformans (sequence type [ST]5), which was significantly less common in HIV-infected individuals. Aiming to compare the phenotypic characteristics of ST5 and non-ST5 C. neoformans, we selected 30 representative Vietnamese isolates and compared their in vitro pathogenic potential and in vivo virulence. ST5 and non-ST5 organisms exhibited comparable characteristics with respect to in vitro virulence markers including melanin production, replication at 37°C, and growth in cerebrospinal fluid. However, the ST5 isolates had significantly increased variability in cellular and capsular sizing compared with non-ST5 organisms (P < .001). Counterintuitively, mice infected with ST5 isolates had significantly longer survival with lower fungal burdens at day 7 than non-ST5 isolates. Notably, ST5 isolates induced significantly greater initial inflammatory responses than non-ST5 strains, measured by TNF-α concentrations (P < .001). Despite being generally less virulent in the mouse model, we hypothesize that the significant within strain variation seen in ST5 isolates in the tested phenotypes may represent an evolutionary advantage enabling adaptation to novel niches including apparently immunocompetent human hosts.
摘要：
我们以前观察到越南的隐球菌性脑膜炎在未感染人类免疫缺陷病毒（HIV）的个体中非典型出现的负担很大。这种疾病与新生隐球菌的单一基因型（序列类型[ST]5）有关，这在HIV感染者中明显不常见。为了比较ST5和非ST5新花虫的表型特征，我们选择了30个具有代表性的越南分离株，并比较了它们的体外致病潜力和体内毒力。ST5和非ST5生物体在体外毒力标记包括黑色素产生方面表现出可比的特征，在37°C复制，和脑脊液的生长。然而,与非ST5生物相比，ST5分离株的细胞和荚膜大小的变异性显着增加（P<.001）。反直觉,感染ST5分离株的小鼠在第7天的存活时间明显长于非ST5分离株，真菌负荷较低。值得注意的是,ST5分离株诱导显著高于非ST5菌株的初始炎症反应，通过TNF-α浓度测量(P<.001)。尽管在小鼠模型中通常毒性较小，我们假设,在测试表型的ST5分离株中观察到的显著菌株内变异可能代表了一种进化优势,能够适应新的生态位,包括具有明显免疫能力的人类宿主.
