铁的获取对于病原体在侵入性感染期间增殖至关重要,人类真菌病原体白色念珠菌也不例外。铁监管网络,在参考菌株SC5314及其衍生物中建立,包括中心参与者Sef1,它是响应铁限制而激活铁获取基因的转录因子。这里,我们通过突变分析探索了五种不同白色念珠菌菌株在该网络中的潜在变异,Nanostring基因表达谱,and,对于两个菌株,RNA-Seq.我们的发现强调了四个特征,这些特征可能会为该物种的自然变异和铁获取的未来研究提供信息。(I)符合性:在所有菌株中,在铁限制期间,主要的铁获取基因被上调,sef1Δ/Δ突变会损害铁限制期间的反应和生长。(ii)响应变化:铁限制响应的某些方面因菌株而异,特别是菌丝相关基因的激活。因为这个基因集与组织损伤和毒力有关,变异可能会影响感染的进展。(iii)基因型-表型变异:sef1Δ/Δ突变对细胞壁完整性的影响各不相同,对于这两个菌株,检查了与sef1Δ/Δ对几个细胞壁完整性基因的影响相关的表型。(iv)表型发现:在sef1Δ/Δ突变体中,铁限制适度诱导了DNA修复基因,随着褶皱的变化,我们通常会忽略。然而,反应发生在测试的两个菌株中,让人想起新生隐球菌中描述的更强的反应,暗示它可能有生物学意义。事实上,我们观察到sef1Δ/Δ突变体的铁限制导致隐性表型出现在两个杂合基因座。总的来说,我们的研究结果表明,对病原体增殖至关重要的网络存在其核心功能之外的变异。重要白色念珠菌的关键毒力因子是在铁缺乏的宿主中维持铁稳态的能力。我们专注于中央铁调节器,SEF1.我们发现铁调节剂Sef1是生长所必需的,细胞壁完整性,和铁限制期间的基因组完整性。这项工作的新颖方面是表征在宿主中存活所需的回路中的菌株变异,以及将铁获取与白色念珠菌基因组完整性联系起来。
Iron acquisition is critical for pathogens to proliferate during invasive infection, and the human fungal pathogen Candida albicans is no exception. The iron regulatory network, established in reference strain SC5314 and derivatives, includes the central player Sef1, a transcription factor that activates iron acquisition genes in response to iron limitation. Here, we explored potential variation in this network among five diverse C. albicans strains through mutant analysis, Nanostring gene expression profiling, and, for two strains, RNA-Seq. Our findings highlight four features that may inform future studies of natural variation and iron acquisition in this species. (i) Conformity: In all strains, major iron acquisition genes are upregulated during iron limitation, and a sef1Δ/Δ mutation impairs that response and growth during iron limitation. (ii) Response variation: Some aspects of the iron limitation response vary among strains, notably the activation of hypha-associated genes. As this gene set is tied to tissue damage and virulence, variation may impact the progression of infection. (iii) Genotype-phenotype variation: The impact of a sef1Δ/Δ mutation on cell wall integrity varies, and for the two strains examined the phenotype correlated with sef1Δ/Δ impact on several cell wall integrity genes. (iv) Phenotype discovery: DNA repair genes were induced modestly by iron limitation in sef1Δ/Δ mutants, with fold changes we would usually ignore. However, the response occurred in both strains tested and was reminiscent of a much stronger response described in Cryptococcus neoformans, a suggestion that it may have biological meaning. In fact, we observed that the iron limitation of a sef1Δ/Δ mutant caused recessive phenotypes to emerge at two heterozygous loci. Overall, our results show that a network that is critical for pathogen proliferation presents variation outside of its core functions.IMPORTANCEA key virulence factor of Candida albicans is the ability to maintain iron homeostasis in the host where iron is scarce. We focused on a central iron regulator, SEF1. We found that iron regulator Sef1 is required for growth, cell wall integrity, and genome integrity during iron limitation. The novel aspect of this work is the characterization of strain variation in a circuit that is required for survival in the host and the connection of iron acquisition to genome integrity in C. albicans.