Juárez-Cepeda Jacqueline, Orta-Zavalza Emmanuel, Cañas-Villamar Israel, Arreola-Gómez Jorge, Pérez-Cornejo Gloria Patricia, Hernández-Carballo Carmen Yudith, Gutiérrez-Escobedo Guadalupe, Castaño Irene, De Las Peñas Alejandro
División de Biología Molecular, Instituto Potosino de Investigación Científica y Tecnológica, IPICYT, Camino a la Presa San José, #2055, Col. Lomas 4ª sección., 78216, San Luis Potosí, San Luis Potosí, Mexico.
Laboratorio de Biofísica, Instituto de Física, Universidad Autónoma de San Luis Potosí, Av. Manuel Nava # 6, Zona Universitaria, 78290, San Luis Potosí, San Luis Potosí, Mexico.
Curr Genet. 2015 Nov;61(4):529-44. doi: 10.1007/s00294-015-0473-2. Epub 2015 Jan 14.
Candida glabrata has emerged as an important opportunistic pathogen in both mucosal and bloodstream infections. C. glabrata contains 67 adhesin-like glycosylphosphatidylinositol-cell-wall proteins (GPI-CWPs), which are classified into seven groups and the largest is the Epa family. Epa proteins are very diverse and their expression is differentially regulated. Like many of the EPA genes, EPA2 is localized in a subtelomeric region where it is subject to chromatin-based transcriptional silencing and its role remains largely unexplored. In this study, we show that EPA2 gene is induced specifically in vitro in the presence of oxidative stress generated by H2O2. This induction is dependent on both Yap1 and Skn7, whereas Msn4 represses EPA2 expression. Interestingly, EPA2 is not induced during phagocytosis, but its expression can be identified in the liver in a murine model of systemic infection. Epa2 has no effect on the virulence of C. glabrata. The work presented herein provides a foundation for future studies to dissect the molecular mechanism(s) by which EPA2 of C. glabrata can be induced in the presence of oxidative stress in a region subject to subtelomeric silencing.
光滑念珠菌已成为黏膜感染和血流感染中一种重要的机会致病菌。光滑念珠菌含有67种黏附素样糖基磷脂酰肌醇细胞壁蛋白(GPI-CWPs),这些蛋白被分为七组,其中最大的一组是Epa家族。Epa蛋白非常多样,其表达受到差异调节。与许多EPA基因一样,EPA2定位于亚端粒区域,在该区域它会受到基于染色质的转录沉默,其作用在很大程度上仍未被探索。在本研究中,我们表明EPA2基因在H2O2产生的氧化应激存在下在体外被特异性诱导。这种诱导依赖于Yap1和Skn7,而Msn4抑制EPA2的表达。有趣的是,EPA2在吞噬作用过程中不被诱导,但其表达可在系统性感染小鼠模型的肝脏中被检测到。Epa2对光滑念珠菌的毒力没有影响。本文所呈现的工作为未来研究剖析光滑念珠菌的EPA2在亚端粒沉默区域的氧化应激存在下可被诱导的分子机制奠定了基础。