Differential activation of a Candida albicans virulence gene family during infection
Differential activation of a Candida albicans virulence gene family during infection
复制标题
DOI：
10.1073/pnas.110031497
复制
发表时间：
2000-05-23
影响因子：
11.1
通讯作者：
Morschhäuser, J
中科院分区：
文献类型：
--
作者：
Staib, P;Kretschmar, M;Morschhäuser, J
白色念珠菌对大多数健康人来说是一种无害的共生菌，但它会在免疫功能低下的患者中引起浅表感染以及危及生命的全身感染。白色念珠菌可以定殖或感染几乎所有身体部位，因为它对不同宿主生态位具有高度适应性，这涉及响应复杂的环境信号而激活适当的基因组。我们使用基于基因重组的体内表达技术作为基因表达的报告基因，以监测编码分泌性天冬氨酸蛋白酶（Saps）的基因家族各个成员在感染过程的各个阶段的差异激活，这些酶与白色念珠菌的毒力有关。我们的结果表明，SAP 表达取决于感染类型，与粘膜感染相比，在全身性疾病期间激活不同的 SAP 同基因。此外，单个 SAP 基因的激活取决于感染的进展，该基因家族的一些成员在与宿主接触后立即被诱导，而其他成员仅在传播到深层器官后才表达。在后一种情况下，入侵生物体的数量决定了毒力基因的诱导是否是成功感染所必需的。体内表达技术可以阐明真菌与宿主相互作用的不同阶段的基因表达模式，从而揭示使白色念珠菌成为人类最成功的真菌病原体的调节适应机制，同时确定某些毒力基因可能发挥作用的感染阶段。
The yeast Candida albicans is a harmless commensal in most healthy people, but it causes superficial as well as life-threatening systemic infections in immunocompromised patients. C. albicans can colonize or infect virtually all body sites because of its high adaptability to different host niches, which involves the activation of appropriate sets of genes in response to complex environmental signals. we have used an in vivo expression technology that is based on genetic recombination as a reporter of gene expression to monitor the differential activation of individual members of a gene family encoding secreted aspartic proteinases (Saps), which have been implicated in C. albicans virulence, at various stages of the infection process. Our results demonstrate that SAP expression depends on the type of infection, with different SAP isogenes being activated during systemic disease as compared with mucosal infection. In addition, the activation of individual SAP genes depends on the progress of the infection, some members of the gene family being induced immediately after contact with the host, whereas others are expressed only after dissemination into deep organs. In the latter case, the number of invading organisms determines whether induction of a virulence gene is necessary for successful infection. The in vivo expression technology allows the elucidation of gene expression patterns at different stages of the fungus-host interaction, thereby revealing regulatory adaptation mechanisms that make C, albicans the most successful fungal pathogen of humans and, at the same time, identifying the stage of an infection at which certain virulence genes may play a role.