Limited Role of Secreted Aspartyl Proteinases Sap1 to Sap6 in Candida albicans Virulence and Host Immune Response in Murine Hematogenously Disseminated Candidiasis
Limited Role of Secreted Aspartyl Proteinases Sap1 to Sap6 in Candida albicans Virulence and Host Immune Response in Murine Hematogenously Disseminated Candidiasis
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DOI：
10.1128/iai.00248-10
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发表时间：
2010-11-01
影响因子：
3.1
通讯作者：
Pais, Celia
中科院分区：
文献类型：
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作者：
Correia, Alexandra;Lermann, Ulrich;Pais, Celia
白念珠菌分泌的唾液酸蛋白酶（Saps）被认为是毒力相关因子。Sap家族的几个成员被认为在通过血源性途径建立的念珠菌病的进展中起重要作用。这一假设是基于观察到的sap无效突变株的毒力减弱。然而，SAP基因对其减毒表型的唯一贡献未得到明确证实，因为这些突变株的Ura状态也可能有助于减毒。在这项研究中，我们重新评估了SAP 1 SAP 6的重要性，在小鼠模型的血源性播散性念珠菌病使用SAP无效突变株不影响其URA 3基因的表达，并比较其毒力表型与URA-blaster SAP突变体。静脉内感染缺乏SAP 1至SAP 3的突变株的BALB/c小鼠的中位生存时间与感染野生型菌株SC 5314的小鼠相当，而感染缺乏SAP 5的突变株的小鼠的生存时间略有延长。然而，在野生型和Δ sap 456突变体之间没有观察到它们侵入小鼠肾脏的能力的差异。同样，SAP 4至SAP 6的缺陷对C.白色念珠菌感染的小鼠。这些结果与相当的乌拉-爆破突变体的行为，这提出了一个显着降低毒力。我们的研究结果表明，Sap 1至Sap 6在C.白念珠菌在血源性播散性念珠菌病小鼠模型中的毒力，并且在该模型中，Sap 1至Sap 3不是成功的白念珠菌所必需的。白色念珠菌感染
Candida albicans secreted aspartyl proteinases (Saps) are considered virulence-associated factors. Several members of the Sap family were claimed to play a significant role in the progression of candidiasis established by the hematogenous route. This assumption was based on the observed attenuated virulence of sap-null mutant strains. However, the exclusive contribution of SAP genes to their attenuated phenotype was not unequivocally confirmed, as the Ura status of these mutant strains could also have contributed to the attenuation. In this study, we have reassessed the importance of SAP1 to SAP6 in a murine model of hematogenously disseminated candidiasis using sap-null mutant strains not affected in their URA3 gene expression and compared their virulence phenotypes with those of Ura-blaster sap mutants. The median survival time of BALB/c mice intravenously infected with a mutant strain lacking SAP1 to SAP3 was equivalent to that of mice infected with wild-type strain SC5314, while those infected with mutant strains lacking SAP5 showed slightly extended survival times. Nevertheless, no differences could be observed between the wild type and a Delta sap456 mutant in their abilities to invade mouse kidneys. Likewise, a deficiency in SAP4 to SAP6 had no noticeable impact on the immune response elicited in the spleens and kidneys of C. albicans-infected mice. These results contrast with the behavior of equivalent Ura-blaster mutants, which presented a significant reduction in virulence. Our results suggest that Sap1 to Sap6 do not play a significant role in C. albicans virulence in a murine model of hematogenously disseminated candidiasis and that, in this model, Sap1 to Sap3 are not necessary for successful C. albicans infection.