Recapitulation of the sexual cycle of the primary fungal pathogen Cryptococcus neoformans var. gattii:: Implications for an outbreak on Vancouver Island, Canada
Recapitulation of the sexual cycle of the primary fungal pathogen Cryptococcus neoformans var. gattii:: Implications for an outbreak on Vancouver Island, Canada
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DOI：
10.1128/ec.2.5.1036-1045.2003
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发表时间：
2003-10-01
期刊：
影响因子：
--
通讯作者：
Heitman, J
中科院分区：
文献类型：
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作者：
Fraser, JA;Subaran, RL;Heitman, J
新型隐球菌是一种人类真菌病原体，存在三种不同的变种或姊妹种：主要的机会致病菌C。新形变种neoformans（血清型D）和C.新形变种grubii（血清型A）和主要病原C.新形变种格特氏（gattii）（血清型B和C）。虽然血清型A和D是世界性的，但血清型B和C通常限于热带地区。B型C.新形变种gattii最近在加拿大的温哥华岛引起了疫情，突出了这种真菌的威胁及其感染免疫能力强的个体的能力。在这里，我们报告了一个大规模的分析交配能力的血清型B和C分离株从不同的来源，并确定不寻常的菌株，交配强劲，适合进一步的遗传分析。与大多数分离株不同，大多数分离株都是a和α交配型，但主要是不育的，而大多数温哥华爆发菌株只属于α交配型，大多数是可育的。在努力提高这些菌株的交配，我们确定和破坏CRG1基因编码的GTP酶激活蛋白参与衰减信息素反应。CRG1突变显著提高了交配效率，并能够与其他不育分离株交配。我们的研究为进一步研究这种主要病原体提供了遗传和分子基础，并揭示了温哥华岛的暴发可能归因于最近的重组事件。
Cryptococcus neoformans is a human fungal pathogen that exists as three distinct varieties or sibling species: the predominantly opportunistic pathogens C. neoformans var. neoformans (serotype D) and C. neoformans var. grubii (serotype A) and the primary pathogen C. neoformans var. gattii (serotypes B and C). While serotypes A and D are cosmopolitan, serotypes B and C are typically restricted to tropical regions. However, serotype B isolates of C. neoformans var. gattii have recently caused an outbreak on Vancouver Island in Canada, highlighting the threat of this fungus and its capacity to infect immunocompetent individuals. Here we report a large-scale analysis of the mating abilities of serotype B and C isolates from diverse sources and identify unusual strains that mate robustly and are suitable for further genetic analysis. Unlike most isolates, which are of both the a and alpha mating types but are predominantly sterile, the majority of the Vancouver outbreak strains are exclusively of the alpha mating type and the majority are fertile. In an effort to enhance mating of these isolates, we identified and disrupted the CRG1 gene encoding the GTPase-activating protein involved in attenuating pheromone response. crg1 mutations dramatically increased mating efficiency and enabled mating with otherwise sterile isolates. Our studies provide a genetic and molecular foundation for further studies of this primary pathogen and reveal that the Vancouver Island outbreak may be attributable to a recent recombination event.