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.

中文翻译：

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评估导致越南艾滋病毒感染者和未感染者脑膜炎的新型隐球菌的毒力。


我们之前观察到，在越南，隐球菌性脑膜炎的严重负担非典型地发生在未感染人类免疫缺陷病毒（HIV）的个体中。这种疾病与单一基因型新型隐球菌（序列类型[ST]5）有关，这种基因型在 HIV 感染者中明显较少见。为了比较 ST5 和非 ST5 新型隐球菌的表型特征，我们选择了 30 个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方面表现出相似的特征，包括黑色素产生、37°C​​ 下的复制和脑脊液中的生长。然而，与非 ST5 生物体相比，ST5 分离株的细胞和荚膜大小的变异性显着增加 (P< .001)。与直觉相反，感染 ST5 分离株的小鼠比非 ST5 分离株的小鼠在第 7 天的存活时间明显更长，且真菌负荷更低。值得注意的是，通过 TNF-α 浓度测量，ST5 菌株比非 ST5 菌株诱导的初始炎症反应明显更强 (P< .001)。尽管在小鼠模型中毒力通常较低，但我们假设在测试表型中 ST5 分离株中观察到的显着株内变异可能代表了一种进化优势，能够适应新的生态位，包括明显具有免疫能力的人类宿主。