Evidence that members of the secretory aspartyl proteinase gene family, in particular SAP2, are virulence factors for Candida vaginitis

Evidence that members of the secretory aspartyl proteinase gene family, in particular SAP2, are virulence factors for Candida vaginitis
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DOI:
10.1086/314546
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发表时间:
1999-01-01
影响因子:
6.4
通讯作者:
Cassone, A
Cassone, A
中科院分区:
医学2区
文献类型:
--
作者:
De Bernardis, F;Arancia, S;Cassone, A

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在雌激素依赖的大鼠阴道炎模型中,研究了靶向破坏分泌天冬氨酸蛋白酶基因(SAP1至SAP6)的白色念珠菌菌株的毒力。sap1 - sap3突变体和sap4 - sap6突变体丧失了亲本菌株SC5314的大部分毒力,特别是sap2突变体在该模型中几乎是无毒的。将SAP2基因重新插入后一种突变体中导致阴道病潜能的恢复。野生型菌株或sap1或sap3突变体感染动物的阴道液在体外表达胃抑素敏感蛋白酶活性。在sap2突变体刺激的大鼠阴道液中没有发现这种活性的痕迹。所有菌株在感染过程中均能产生真菌丝。因此,SAP家族成员,特别是SAP2,在阴道炎中起着明确的致病作用,可能成为这种感染的化学免疫治疗的新靶点。
Virulence of Candida albicans strains with targeted disruption of secretory aspartyl proteinase genes (SAP1 to SAP6) was assessed in an estrogen-dependent rat vaginitis model. Null sap1 to sap3 but not sap4 to sap6 mutants lost most of the virulence of their parental strain SC5314, In particular, the sap2 mutant was almost avirulent in this model. Reinsertion of the SAP2 gene into this latter mutant led to the to recovery of the vaginopathic potential. The vaginal fluids of the animals infected by the wild type strain or by the sap1 or sap3 mutants expressed a pepstatin-sensitive proteinase activity in vitro. No traces of this activity were found in the vaginal fluid of rats challenged by the sap2 mutant. All strains were capable of developing true hyphae during infection. Thus, members of SAP family, in particular SAP2, play a clear pathogenic role in vaginitis and may constitute a novel target for chemoimmunotherapy of this infection.