Antifungal susceptibility of new genotype of Candida albicans strains with group 1 intron

利用特异性PCR引物扩增的DNA条带长度，对日本和泰国临床分离的白色念珠菌进行了遗传多样性研究。401株临床分离的白色念珠菌可分为A、B、C、D（都柏林念珠菌）五种基因型和一种新的E基因型。来自日本和泰国的菌株大多为A型，C型为少数。基因型E的特征在于具有组1内含子样序列，其比迄今报道的更长，并且具有962-bp的核苷酸序列长度。对962 bp序列的分析表明，它由一个类似于都柏林隐球菌的621 bp的内含子和一个341 bp的插入组成。ITS区序列分析表明，该基因与白色念珠菌的ITS区序列完全一致。通过研究，推测第1组内含子在都柏林念珠菌和白色念珠菌之间可能存在水平转移。观察到基因型E中I组内含子的存在与对氟胞嘧啶的敏感性之间高度相关。分别来自日本和泰国的5个和2个菌株。它们不是从艾滋病患者中分离出来的，对唑类抗真菌药如氟康唑也不耐药。日本和泰国的耐药菌株多为A、B、r、C基因型。本实验室利用自制的微阵列系统，用微阵列技术分析了白念珠菌（非都柏林念珠菌）对唑类和氟胞嘧啶类抗真菌药的耐药机制。

The genetic diversity of recent clinical isolates of Candida albicans in Japan and Thailand was studied on the basis of amplified DNA band lengths determined with a specific PCR Primer. Our analyses of 401 clinical isolates of C.albicans showed that they could be classified into five genotypes A, B, C, D (C.dubliniensis) and a new genotype E. Most of the strains from Japan as well as Thailand were genotype A, and C was a minor group. The genotype E was characterized to have a group 1 intron-like sequence, which is longer that hitherto reported ones ad which has a nucleotide sequence length of 962-bp. Our analysis of the 962-bp sequence indicated that it is composed of an intron similar to that of C.dubliniensis of 621-bp with a 341-bp insertion. Analysis of the sequence of ITS region of the E showed that the sequence is identical with those of C.albicans. Throught the study, the possible horizontal transfer of the group 1 intron between C.dubliniensis and C.albicans E was suggested. A high degree of correlation between the presence of group l intron in genotype E and the susceptibility to flucytosine was observed. Five and two strains of C.dubliniensis from Japan and Thailand, respectively. They were not isolates from AIDS patients, and not resistant to azole-type antifungals such as fluconazole. Most of the resistant strains were found to belong to genotype A, B, o r, C, in Japan and Thailand. Detailed mechanisms of resistant of C.albicans (not C.dubliniensis) to azole and flucytosine ant ifungals were analyzed using micro-array method using home made array system in our laboratory.