Warenda Amy J, Kauffman Sarah, Sherrill Taylor P, Becker Jeffrey M, Konopka James B
Department of Molecular Genetics and Microbiology, State University of New York, Stony Brook, New York 11794-5222, USA.
Infect Immun. 2003 Jul;71(7):4045-51. doi: 10.1128/IAI.71.7.4045-4051.2003.
Hyphal growth of Candida albicans is implicated as an important virulence factor for this opportunistic human pathogen. Septin proteins, a family of cytoskeletal elements that regulate membrane events and are important for proper morphogenesis of C. albicans, were examined for their role in tissue invasion and virulence in the mouse model of systemic infection. In vitro, septin mutants are only mildly defective for hyphal growth in liquid culture but display pronounced defects for invasive growth into agar. In vivo, the septin mutants were found to exhibit attenuated virulence. However, mice infected with the mutants displayed high fungal burdens in their kidneys without obvious symptoms of disease. Histological examination of infected kidneys revealed defects in organ invasion for the cdc10 Delta and cdc11 Delta deletion mutants, which displayed both reduced tissue penetration and noninvasive fungal masses. Thus, the septin proteins are necessary for invasive growth, which appears to be more important to the successful pathogenesis of C. albicans than hyphal growth alone.
白色念珠菌的菌丝生长被认为是这种人类机会致病菌的一个重要毒力因子。Septin蛋白是一类细胞骨架成分,可调节膜相关事件,对白色念珠菌的正常形态发生很重要,本研究检测了它们在系统性感染小鼠模型中的组织侵袭和毒力方面的作用。在体外,septin突变体在液体培养中菌丝生长仅存在轻微缺陷,但在侵入琼脂生长方面表现出明显缺陷。在体内,发现septin突变体的毒力减弱。然而,感染突变体的小鼠肾脏中真菌负荷很高,但没有明显的疾病症状。对感染肾脏的组织学检查发现,cdc10Δ和cdc11Δ缺失突变体在器官侵袭方面存在缺陷,表现为组织穿透力降低和非侵袭性真菌团块。因此,septin蛋白对于侵袭性生长是必需的,这似乎对白色念珠菌的成功致病比单纯的菌丝生长更为重要。