Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, SP, Brazil.
Int J Mol Sci. 2023 Dec 28;25(1):405. doi: 10.3390/ijms25010405.
is the primary causative agent of dermatophytosis worldwide. This fungus colonizes keratinized tissues and uses keratin as a nutritional source during infection. In -host interactions, sensing a hostile environment triggers the adaptation of its metabolic machinery to ensure its survival. The glyoxylate cycle has emerged as an alternative metabolic pathway when glucose availability is limited; this enables the conversion of simple carbon compounds into glucose via gluconeogenesis. In this study, we investigated the impact of deletion on the response of glyoxylate cycle enzymes during fungal growth under varying culture conditions in conjunction with post-transcriptional regulation through alternative splicing of the genes encoding these enzymes. We revealed that the Δ mutant downregulated the malate synthase and isocitrate lyase genes in a keratin-containing medium or when co-cultured with human keratinocytes. Alternative splicing of an isocitrate lyase gene yielded a new isoform. Enzymatic activity assays showed specific instances where isocitrate lyase and malate synthase activities were affected in the mutant strain compared to the wild type strain. Taken together, our results indicate a relevant balance in transcriptional regulation that has distinct effects on the enzymatic activities of malate synthase and isocitrate lyase.
是全球范围内皮肤癣菌病的主要病原体。这种真菌定植于角蛋白组织，并在感染过程中利用角蛋白作为营养来源。在宿主内相互作用中，感知到敌对环境会触发其代谢机制的适应性变化，以确保其存活。当葡萄糖供应有限时，乙醛酸循环已成为一种替代代谢途径；这使得通过糖异生将简单的碳化合物转化为葡萄糖。在这项研究中，我们研究了在不同培养条件下，当葡萄糖可用性有限时，基因缺失对乙醛酸循环酶在真菌生长过程中的反应的影响，以及通过这些酶的基因转录后剪接的替代来进行的调控。我们揭示了在角蛋白存在的培养基中或与人角质形成细胞共培养时，Δ突变体下调了苹果酸合酶和异柠檬酸裂解酶基因的表达。异柠檬酸裂解酶基因的转录后剪接产生了一种新的同工酶。酶活性测定显示，与野生型菌株相比，突变菌株中的异柠檬酸裂解酶和苹果酸合酶活性在特定情况下受到影响。综上所述，我们的结果表明转录调控中的一个相关平衡，对苹果酸合酶和异柠檬酸裂解酶的酶活性有明显的影响。
