Zhou Yujie, Cheng Lei, Liao Binyou, Shi Yangyang, Niu Yulong, Zhu Chengguang, Ye Xingchen, Zhou Xuedong, Ren Biao
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, 610041, Sichuan, China.
Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China.
Appl Microbiol Biotechnol. 2021 Mar;105(6):2485-2496. doi: 10.1007/s00253-021-11187-0. Epub 2021 Feb 26.
The roles of Candida albicans CHK1, a key gene from two-component system, in oral mucosal infection are not clear. This study evaluated the key roles of CHK1 gene in vitro and in vivo. The expression of CHK1 and its regulated virulence factors were tested during the oral epithelial cell infection. The production of lactate dehydrogenase, ROS, and IL-1α combined with the confocal and scanning electron microscope observation was employed to identify the capability of CHK1 in damaging the epithelial cells. Both immunocompetent and immunodeficient mice oropharyngeal infection models were involved to confirm the roles of CHK1 gene in vivo. The expression of CHK1 gene was significantly increased during the oral epithelial cell infection. The chk1Δ/Δ mutant failed to damage the epithelial cells or induce IL-α and ROS production. Interestingly, chk1Δ/Δ can also form the similar hyphae with WT and complementary strains. Accordingly, chk1Δ/Δ did not affect the adhesion and invasion rates of C. albicans to oral epithelial cells. However, chk1Δ/Δ significantly decreased the expression levels of the virulence factors, including ALS2, SAP6, and YWP1. The chk1Δ/Δ also failed to cause oral candidiasis in both immunocompetent and immunodeficient mice indicating that CHK1 gene from the two-component system is essential for the pathogenicity of C. albicans. KEY POINTS: • CHK1gene is essential for C. albicans in oral candidiasis • C. albicans without CHK1 gene can form "non-pathogenic" hyphae. • CHK1 gene regulates the virulence of C. albicans.
白色念珠菌CHK1是双组分系统中的关键基因，其在口腔黏膜感染中的作用尚不清楚。本研究评估了CHK1基因在体外和体内的关键作用。在口腔上皮细胞感染过程中检测了CHK1的表达及其调控的毒力因子。采用乳酸脱氢酶、活性氧和白细胞介素-1α的产生，并结合共聚焦显微镜和扫描电子显微镜观察，以确定CHK1破坏上皮细胞的能力。使用免疫健全和免疫缺陷小鼠的口咽感染模型来证实CHK1基因在体内的作用。在口腔上皮细胞感染期间，CHK1基因的表达显著增加。chk1Δ/Δ突变体未能破坏上皮细胞或诱导白细胞介素-α和活性氧的产生。有趣的是，chk1Δ/Δ也能与野生型和互补菌株形成相似的菌丝。因此，chk1Δ/Δ不影响白色念珠菌对口腔上皮细胞的黏附和侵袭率。然而，chk1Δ/Δ显著降低了毒力因子的表达水平，包括ALS2、SAP6和YWP1。chk1Δ/Δ在免疫健全和免疫缺陷小鼠中也未能引起口腔念珠菌病，这表明双组分系统中的CHK1基因对白色念珠菌的致病性至关重要。要点：• CHK1基因对白色念珠菌引起口腔念珠菌病至关重要 • 不含CHK1基因的白色念珠菌可形成“无致病性”的菌丝。• CHK1基因调节白色念珠菌的毒力。
