Bendel C M, Kinneberg K M, Jechorek R P, Gale C A, Erlandsen S L, Hostetter M K, Wells C L
Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota 55455-0385, USA.
Mol Genet Metab. 1999 Aug;67(4):343-51. doi: 10.1006/mgme.1999.2875.
The Candida albicans gene INT1 is associated with epithelial adhesion, hyphal formation, and virulence. C. albicans strains carrying two, one, or no functional INT1 alleles were used to assess the association between mortality and C. albicans persistence in the liver and kidney of intravenously inoculated mice. Mice were injected with 10(5) C. albicans CAF2 (parent strain, INT1/INT1), C. albicans CAG3 (homozygous disruptant, Int1/int1), or C. albicans CAG5 (heterozygous reintegrant, int1/int1 + INT1). Mortality was monitored and mice were sacrificed on Days 1, 7, 14, and 21 for quantitative analysis of kidney and liver microbes, with histologic analysis of these tissues as well. Mortality was highest for mice injected with the wild-type strain CAF2 (INT1/INT1) and lowest for mice injected with the homozygous disruptant CAG3 (int/int1). Yeast were readily cleared from the liver of all mice injected with any of the three C. albicans strains. Although the mutant strains CAG3 and CAG5 are defective for hyphal formation in vitro, there was histological evidence of abundant hyphal formation in the renal pelvis of mice injected with these strains. Compared to the wild-type strain, mutant strains were associated with reduced mortality but increased C. albicans persistence in the kidney. Thus, the absolute ability to form hyphae in the kidney did not appear to modulate either C. albicans-induced mortality or the course of progressive infection in the kidney. In addition, reduced virulence was paradoxically associated with increased, not decreased, persistence of C. albicans in the kidney.
白色念珠菌基因INT1与上皮黏附、菌丝形成及毒力相关。使用携带两个、一个或无功能性INT1等位基因的白色念珠菌菌株，来评估静脉接种小鼠的死亡率与白色念珠菌在肝脏和肾脏中持续存在之间的关联。给小鼠注射10⁵个白色念珠菌CAF2（亲本菌株，INT1/INT1）、白色念珠菌CAG3（纯合缺失株，Int1/int1）或白色念珠菌CAG5（杂合整合株，int1/int1 + INT1）。监测死亡率，并在第1、7、14和21天处死小鼠，以对肾脏和肝脏微生物进行定量分析，同时对这些组织进行组织学分析。注射野生型菌株CAF2（INT1/INT1）的小鼠死亡率最高，注射纯合缺失株CAG3（int/int1）的小鼠死亡率最低。所有注射三种白色念珠菌菌株中任何一种的小鼠肝脏中的酵母都能迅速清除。尽管突变菌株CAG3和CAG5在体外形成菌丝有缺陷，但在注射这些菌株的小鼠肾盂中有大量菌丝形成的组织学证据。与野生型菌株相比，突变菌株与死亡率降低但白色念珠菌在肾脏中持续存在增加有关。因此，在肾脏中形成菌丝的绝对能力似乎并未调节白色念珠菌诱导的死亡率或肾脏中进行性感染的进程。此外，毒力降低反常地与白色念珠菌在肾脏中持续存在增加而非减少相关。
