Elevated aspartic proteinase secretion and experimental pathogenicity of Candida albicans isolates from oral cavities of subjects infected with human immunodeficiency virus
Elevated aspartic proteinase secretion and experimental pathogenicity of Candida albicans isolates from oral cavities of subjects infected with human immunodeficiency virus
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DOI：
10.1128/iai.64.2.466-471.1996
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发表时间：
1996-02-01
影响因子：
3.1
通讯作者：
Cassone, A
中科院分区：
文献类型：
--
作者：
DeBernardis, F;Chiani, P;Cassone, A
对人类免疫缺陷病毒 (HIV) 感染不同阶段的受试者或未感染对照者的口腔中分离的白色念珠菌进行检查，以检测 (i) 天冬氨酸蛋白酶（一种假定的毒力相关因子）的产生； (ii) 真菌基因组中存在天冬氨酸蛋白酶家族的两个主要基因（SAP1 和 SAP2）； (iii)全身感染小鼠模型中的实验致病性。结果发现，来自有症状患者的真菌分离物分泌的蛋白酶平均比来自未感染或感染艾滋病毒但无症状受试者的分离物多八倍。即使在原种培养物中维持多年后，菌株仍能稳定表达这种差异特性。此外，代表性的高蛋白酶分离株对小鼠的致病性明显高于白色念珠菌的低蛋白酶分离株。高蛋白酶和毒力增强的特征与通过 DNA 指纹或脉冲场电泳核型可识别的单一分子类型或类别无关，并且 SAP1 和 SAP2 基因都存在于两类分离株中，位于相同的各自染色体上。总之，我们的数据表明，在 HN 感染期间，选择了可通过毒力决定因素直接分析来识别的毒性更强的白色念珠菌菌株或生物型。似乎在 HIV 感染者进入症状阶段和明显的艾滋病之前，生物型转变为增加的天冬氨酸蛋白酶和毒力特性。
Isolates of Candida albicans from the oral cavities of subjects at different stages of human immunodeficiency virus (HIV) infection or uninfected controls were examined for (i) production of aspartic proteinase(s), a putative virulence-associated factor(s); (ii) the presence in the fungal genome of two major genes (SAP1 and SAP2) of the aspartic proteinase family; and (iii) experimental pathogenicity in a murine model of systemic infection, It was found that the fungal isolates from symptomatic patients secreted, on average, up to eightfold more proteinase than the isolates from uninfected or HIV-infected but asymptomatic subjects. This differential property was stably expressed by the strains even after years of maintenance in stock cultures. Moreover, representative high-proteinase isolates were significantly more pathogenic for mice than low-proteinase isolates of C. albicans. The characters high proteinase and increased virulence were not associated with a single molecular type or category identifiable through DNA fingerprinting or pulsed-field electrophoretic karyotype, and both SAP1 and SAP2 genes were present in both categories of isolates, on the same respective chromosomes. In conclusion, our data suggest that during HN infection more-virulent strains or biotypes of C. albicans which are identifiable by direct analysis of virulence determinants are selected. It also appears that the biotype switch to increased aspartic proteinase and virulence properties occurs before the HIV-infected subject enters the symptomatic stage and overt AIDS.