Rahman Durdana, Mistry Mukesh, Thavaraj Selvam, Challacombe Stephen J, Naglik Julian R
Department of Oral Medicine and Immunology, King's College London Dental Institute at Guy's, King's College and St Thomas' Hospitals, London SE1 9RT, UK.
Microbes Infect. 2007 Apr;9(5):615-22. doi: 10.1016/j.micinf.2007.01.012. Epub 2007 Jan 27.
We report the creation of a new low-estrogen murine model of concurrent oral and vaginal C. albicans colonization that resembles human candidal carriage at both mucosal sites. Weekly estrogen administration of 5 microg intramuscular and subcutaneously was optimal for enhancement of oral colonization and was essential for vaginal colonization. In BALB/c mice, a number of C. albicans clinical isolates (n=3) colonized both oral and/or vaginal sites, but only strain 529L colonized 100% of mice persistently for over 5 weeks. Laboratory strains SC5314 and NCPF 3153 did not colonize the model; however, NCPF 3156 showed vaginal colonization up to week 5. Prior passaging through mice enhanced subsequent colonization of SC5314. Intranasal immunization with a C. albicans virulence antigen (secreted aspartyl proteinase 2) significantly reduced or abolished the fungal burden orally and vaginally by week 2 and 7. Our concurrent model of mucosal colonization reduces the numbers of experimental mice by half, can be used to assess potential vaccine candidates, and permits the detailed analysis of host-fungal interactions during the natural state of Candida colonization.
我们报告创建了一种新的低雌激素小鼠模型,该模型同时存在口腔和阴道白色念珠菌定植,类似于人类在两个黏膜部位的念珠菌携带情况。每周肌肉注射和皮下注射5微克雌激素最有利于增强口腔定植,对阴道定植则必不可少。在BALB/c小鼠中,一些白色念珠菌临床分离株(n = 3)定植于口腔和/或阴道部位,但只有529L菌株在超过5周的时间里持续100%定植于小鼠。实验室菌株SC5314和NCPF 3153未在该模型中定植;然而,NCPF 3156在第5周前均有阴道定植。先前在小鼠体内传代增强了SC5314随后的定植。用白色念珠菌毒力抗原(分泌天冬氨酸蛋白酶2)进行鼻内免疫,到第2周和第7周时,口腔和阴道内的真菌负荷显著降低或消除。我们的黏膜定植并发模型将实验小鼠数量减少了一半,可用于评估潜在的疫苗候选物,并允许在念珠菌定植自然状态下详细分析宿主-真菌相互作用。