De Bernardis F, Chiani P, Ciccozzi M, Pellegrini G, Ceddia T, D'Offizzi G, Quinti I, Sullivan P A, Cassone A
Department of Bacteriology and Medical Mycology, Istituto Superiore di Sanità, Rome, Italy.
Infect Immun. 1996 Feb;64(2):466-71. doi: 10.1128/iai.64.2.466-471.1996.
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 HIV 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.
对来自处于人类免疫缺陷病毒（HIV）感染不同阶段的受试者口腔或未感染对照的白色念珠菌分离株进行了检测，以确定：（i）天冬氨酸蛋白酶的产生，这是一种假定的毒力相关因子；（ii）真菌基因组中天冬氨酸蛋白酶家族两个主要基因（SAP1和SAP2）的存在情况；以及（iii）在系统性感染小鼠模型中的实验致病性。结果发现，有症状患者的真菌分离株平均分泌的蛋白酶比未感染或HIV感染但无症状受试者的分离株多八倍。即使在菌种保藏多年后，这些菌株仍能稳定表达这种差异特性。此外，代表性的高蛋白酶活性分离株对小鼠的致病性明显高于白色念珠菌的低蛋白酶活性分离株。高蛋白酶活性和增加的毒力特征与通过DNA指纹图谱或脉冲场电泳核型鉴定的单一分子类型或类别无关，两类分离株的SAP1和SAP2基因均存在于各自相同的染色体上。总之，我们的数据表明，在HIV感染期间，可通过直接分析毒力决定因素鉴定出的白色念珠菌更具毒力的菌株或生物型被选择出来。似乎在HIV感染受试者进入有症状阶段和明显的艾滋病之前，就发生了生物型转变，转变为天冬氨酸蛋白酶活性增加和毒力特性增强。
