Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America.
PLoS Pathog. 2011 Sep;7(9):e1002205. doi: 10.1371/journal.ppat.1002205. Epub 2011 Sep 1.
Cryptococcus gattii infections in southern California have been reported in patients with HIV/AIDS. In this study, we examined the molecular epidemiology, population structure, and virulence attributes of isolates collected from HIV/AIDS patients in Los Angeles County, California. We show that these isolates consist almost exclusively of VGIII molecular type, in contrast to the VGII molecular type isolates causing the North American Pacific Northwest outbreak. The global VGIII population structure can be divided into two molecular groups, VGIIIa and VGIIIb. Isolates from the Californian patients are virulent in murine and macrophage models of infection, with VGIIIa significantly more virulent than VGIIIb. Several VGIII isolates are highly fertile and produce abundant sexual spores that may serve as infectious propagules. The a and α VGIII MAT locus alleles are largely syntenic with limited rearrangements compared to the known VGI (a/α) and VGII (α) MAT loci, but each has unique characteristics including a distinct deletion flanking the 5' VGIII MATa alleles and the α allele is more heterogeneous than the a allele. Our studies indicate that C. gattii VGIII is endemic in southern California, with other isolates originating from the neighboring regions of Mexico, and in rarer cases from Oregon and Washington state. Given that >1,000,000 cases of cryptococcal infection and >620,000 attributable mortalities occur annually in the context of the global AIDS pandemic, our findings suggest a significant burden of C. gattii may be unrecognized, with potential prognostic and therapeutic implications. These results signify the need to classify pathogenic Cryptococcus cases and highlight possible host differences among the C. gattii molecular types influencing infection of immunocompetent (VGI/VGII) vs. immunocompromised (VGIII/VGIV) hosts.
加利福尼亚南部已有报道称，艾滋病毒/艾滋病患者感染了隐球菌。在这项研究中，我们检查了从加利福尼亚州洛杉矶县艾滋病毒/艾滋病患者中采集的分离物的分子流行病学、种群结构和毒力属性。我们表明，这些分离物几乎完全由 VGIII 分子类型组成，与引起北美太平洋西北暴发的 VGII 分子类型分离物形成对比。全球 VGIII 种群结构可分为两个分子群，VGIIIa 和 VGIIIb。来自加利福尼亚患者的分离物在感染鼠和巨噬细胞的模型中具有毒力，VGIIIa 比 VGIIIb 显著更具毒力。几种 VGIII 分离物具有高度的繁殖力，产生丰富的性孢子，这些孢子可能是传染性的繁殖体。与已知的 VGI（a/α）和 VGII（α）MAT 基因座相比，VGIIIa 和 α VGIII MAT 基因座等位基因在很大程度上是同基因的，只有有限的重排，但每个都具有独特的特征，包括围绕 5' VGIII MATa 等位基因的独特缺失和 α 等位基因比 a 等位基因更具异质性。我们的研究表明，C. gattii VGIII 是加利福尼亚南部的地方病，其他分离物来自墨西哥的邻近地区，在更罕见的情况下来自俄勒冈州和华盛顿州。鉴于在全球艾滋病流行的背景下，每年有超过 100 万例隐球菌感染和超过 62 万例可归因的死亡病例，我们的发现表明，C. gattii 的负担可能未被识别，这可能具有重要的预后和治疗意义。这些结果表明需要对致病性隐球菌病例进行分类，并强调影响免疫功能正常（VGI/VGII）和免疫功能低下（VGIII/VGIV）宿主感染的 C. gattii 分子类型之间可能存在宿主差异。
