Department of Pediatrics, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States of America.
PLoS One. 2011;6(7):e22030. doi: 10.1371/journal.pone.0022030. Epub 2011 Jul 19.
Disseminated candidiasis is the third leading nosocomial blood stream infection in the United States and is often fatal. We previously showed that disseminated candidiasis was preventable in normal mice by immunization with either a glycopeptide or a peptide synthetic vaccine, both of which were Candida albicans cell wall derived. A weakness of these studies is that, unlike humans, mice do not have a C. albicans GI flora and they lack Candida serum antibodies. We examined the influence of C. albicans GI tract colonization and serum antibodies on mouse vaccination responses to the peptide, Fba, derived from fructose bisphosphate aldolase which has cytosolic and cell wall distributions in the fungus. We evaluated the effect of live C. albicans in drinking water and antimicrobial agents on establishment of Candida colonization of the mouse GI tract. Body mass, C. albicans in feces, and fungal-specific serum antibodies were monitored longitudinally. Unexpectedly, C. albicans colonization occurred in mice that received only antibiotics in their drinking water, provided that the mice were housed in the same room as intentionally colonized mice. The fungal strain in unintentionally colonized mice appeared identical to the strain used for intentional GI-tract colonization. This is the first report of horizontal transmission and spontaneous C. albicans colonization in mice. Importantly, many Candida-colonized mice developed serum fungal-specific antibodies. Despite the GI-tract colonization and presence of serum antibodies, the animals made antibodies in response to the Fba immunogen. This mouse model has potential for elucidating C. albicans horizontal transmission and for exploring factors that induce host defense against disseminated candidiasis. Furthermore, a combined protracted GI-tract colonization with Candida and the possibility of serum antibody responses to the presence of the fungus makes this an attractive mouse model for testing the efficacy of vaccines designed to prevent human disseminated candidiasis.
播散性念珠菌病是美国第三大医院获得性血流感染，通常是致命的。我们之前的研究表明，在正常小鼠中，通过用糖肽或肽合成疫苗进行免疫，可以预防播散性念珠菌病，这两种疫苗均来自白念珠菌细胞壁。这些研究的一个弱点是，与人类不同，小鼠没有白念珠菌胃肠道菌群，也缺乏念珠菌血清抗体。我们研究了白念珠菌胃肠道定植和血清抗体对来源于果糖二磷酸醛缩酶的肽（Fba）疫苗接种反应的影响，该肽在真菌中具有细胞质和细胞壁分布。我们评估了饮用水中的活白念珠菌和抗菌剂对建立小鼠胃肠道念珠菌定植的影响。体重、粪便中的白念珠菌和真菌特异性血清抗体被纵向监测。出乎意料的是，即使在饮用水中只接受抗生素的小鼠中，也会发生白念珠菌定植，只要这些小鼠与故意定植的小鼠饲养在同一房间中。无意中定植的小鼠中的真菌菌株与用于故意胃肠道定植的菌株相同。这是首例报道的小鼠水平传播和自发白念珠菌定植。重要的是，许多念珠菌定植的小鼠产生了针对真菌的血清抗体。尽管存在胃肠道定植和血清抗体，动物仍能对 Fba 免疫原产生抗体。这种小鼠模型具有阐明白念珠菌水平传播和探索诱导宿主对播散性念珠菌病产生防御的因素的潜力。此外，白念珠菌在胃肠道中的长期定植以及血清抗体对真菌存在的反应的可能性，使得该模型成为一种有吸引力的小鼠模型，可用于测试旨在预防人类播散性念珠菌病的疫苗的疗效。
