Lim Joo-Yeon, Jung Ye-Eun, Hwang Hye-Eun, Kim Cheol-Hee, Basaran-Akgul Nese, Goli Sri Harshini, Templeton Steven P, Park Hee-Moon
Department of Microbiology and Immunology, Indiana University School of Medicine-Terre Haute, Terre Haute, IN 47807, USA.
Laboratory of Cellular Differentiation, Department of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University, Daejeon 34134, Republic of Korea.
J Fungi (Basel). 2023 Jan 21;9(2):143. doi: 10.3390/jof9020143.
Survival factor A (SvfA) in plays multiple roles in growth and developmental processes. It is a candidate for a novel VeA-dependent protein involved in sexual development. VeA is a key developmental regulator in species that can interact with other velvet-family proteins and enter into the nucleus to function as a transcription factor. In yeast and fungi, SvfA-homologous proteins are required for survival under oxidative and cold-stress conditions. To assess the role of SvfA in virulence in , cell wall components, biofilm formation, and protease activity were evaluated in a -gene-deletion or an overexpressing strain. The -deletion strain showed decreased production of β-1,3-glucan in conidia, a cell wall pathogen-associated molecular pattern, with a decrease in gene expression for chitin synthases and β-1,3-glucan synthase. The ability to form biofilms and produce proteases was reduced in the -deletion strain. We hypothesized that the -deletion strain was less virulent than the wild-type strain; therefore, we performed in vitro phagocytosis assays using alveolar macrophages and analyzed in vivo survival using two vertebrate animal models. While phagocytosis was reduced in mouse alveolar macrophages challenged with conidia from the -deletion strain, the killing rate showed a significant increase with increased extracellular signal-regulated kinase ERK activation. The -deletion conidia infection reduced host mortality in both T-cell-deficient zebrafish and chronic granulomatous disease mouse models. Taken together, these results indicate that SvfA plays a significant role in the pathogenicity of .
生存因子A（SvfA）在生长和发育过程中发挥多种作用。它是一种参与有性发育的新型VeA依赖性蛋白的候选物。VeA是某些物种中的关键发育调节因子，可与其他天鹅绒家族蛋白相互作用并进入细胞核发挥转录因子的作用。在酵母和真菌中，SvfA同源蛋白是氧化和冷应激条件下生存所必需的。为了评估SvfA在某物种毒力中的作用，在基因缺失或过表达菌株中评估了细胞壁成分、生物膜形成和蛋白酶活性。该基因缺失菌株分生孢子中β-1,3-葡聚糖的产量降低，β-1,3-葡聚糖是一种细胞壁病原体相关分子模式，几丁质合成酶和β-1,3-葡聚糖合成酶的基因表达也降低。该基因缺失菌株形成生物膜和产生蛋白酶的能力降低。我们假设该基因缺失菌株的毒力低于野生型菌株；因此，我们使用肺泡巨噬细胞进行了体外吞噬试验，并使用两种脊椎动物动物模型分析了体内存活率。在用该基因缺失菌株的分生孢子攻击的小鼠肺泡巨噬细胞中，吞噬作用降低，而随着细胞外信号调节激酶ERK激活增加，杀伤率显著增加。该基因缺失分生孢子感染在T细胞缺陷的斑马鱼和慢性肉芽肿病小鼠模型中均降低了宿主死亡率。综上所述，这些结果表明SvfA在某物种的致病性中起重要作用。
