Host Defense Mechanisms Induce Genome Instability Leading to Rapid Evolution in an Opportunistic Fungal Pathogen
Host Defense Mechanisms Induce Genome Instability Leading to Rapid Evolution in an Opportunistic Fungal Pathogen
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DOI：
10.1128/iai.00328-21
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发表时间：
2021-12
影响因子：
3.1
通讯作者：
Amanda C. Smith;Levi T. Morran;Meleah A. Hickman
中科院分区：
文献类型：
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作者：
Amanda C. Smith;Levi T. Morran;Meleah A. Hickman
产生遗传变异的能力有助于在压力环境中快速适应。机会致病真菌白念珠菌暴露于宿主环境后，经常发生大规模的基因组变化，包括非整倍体和杂合性缺失（洛）。产生遗传变异的能力促进了在压力环境中的快速适应。机会致病真菌白念珠菌暴露于宿主环境后，经常发生大规模的基因组变化，包括非整倍体和杂合性缺失（洛）。然而，诱导C.白念珠菌基因组的不稳定性仍然是未知的。在这里，我们利用线虫宿主的遗传易处理性来研究先天免疫成分，包括抗菌肽（AMP）和活性氧（ROS），是否诱导宿主相关的C。白念珠菌基因组不稳定性C.与免疫活性宿主相关的白念珠菌携带多个大规模的基因组变化，包括洛缺失和全染色体和节段性非整倍体。与之相反，C.与AMP或ROS产生缺陷的免疫受损宿主相关的白色念珠菌的洛频率降低，并且即使有额外的基因组变化，也较少。为了评估广泛的宿主诱导的基因组变化是否对C. albicans适应，我们实验进化了C.白念珠菌在免疫活性或免疫功能低下的宿主和选择增加毒力。C.在免疫活性宿主中进化的白色念珠菌毒力迅速增强，但C.在免疫功能低下的宿主中进化的白色念珠菌则没有。总之，这项工作表明，宿主产生的ROS和AMP诱导C。白色念珠菌，促进快速进化。
The ability to generate genetic variation facilitates rapid adaptation in stressful environments. The opportunistic fungal pathogen Candida albicans frequently undergoes large-scale genomic changes, including aneuploidy and loss of heterozygosity (LOH), following exposure to host environments. ABSTRACT The ability to generate genetic variation facilitates rapid adaptation in stressful environments. The opportunistic fungal pathogen Candida albicans frequently undergoes large-scale genomic changes, including aneuploidy and loss of heterozygosity (LOH), following exposure to host environments. However, the specific host factors inducing C. albicans genome instability remain largely unknown. Here, we leveraged the genetic tractability of nematode hosts to investigate whether innate immune components, including antimicrobial peptides (AMPs) and reactive oxygen species (ROS), induced host-associated C. albicans genome instability. C. albicans associated with immunocompetent hosts carried multiple large-scale genomic changes, including LOH and whole-chromosomal and segmental aneuploidies. In contrast, C. albicans associated with immunocompromised hosts deficient in AMPs or ROS production had reduced LOH frequencies and fewer, if any, additional genomic changes. To evaluate whether extensive host-induced genomic changes had long-term consequences for C. albicans adaptation, we experimentally evolved C. albicans in either immunocompetent or immunocompromised hosts and selected for increased virulence. C. albicans evolved in immunocompetent hosts rapidly increased virulence, but C. albicans evolved in immunocompromised hosts did not. Taken together, this work suggests that host-produced ROS and AMPs induces genotypic plasticity in C. albicans which facilitates rapid evolution.