Homozygosity at the MTL locus in clinical strains of Candida albicans:: karyotypic rearrangements and tetraploid formation

Homozygosity at the MTL locus in clinical strains of Candida albicans:: karyotypic rearrangements and tetraploid formation
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DOI:
10.1111/j.1365-2958.2004.04068.x
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发表时间:
2004-06-01
影响因子:
3.6
通讯作者:
Magee, BB
Magee, BB
中科院分区:
生物学2区
文献类型:
--
作者:
Legrand, M;Lephart, P;Magee, BB

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从20世纪80年代末和90年代初的120白色念珠菌临床分离株进行了检查MTL基因座的纯合性。其中,108例为杂合子(MTLa/MTL α),7例为MTLa,5例为MTL α。其中5个纯合分离株能够转变为不透明细胞形态,而其余7个分离株中未检测到不透明细胞。然而,所有的,但在MTL基因座纯合的分离物之一,显示交配,并产生含有来自父母双方的标记的细胞,非mater被发现有一个移码MTLalpha 1基因。与酿酒酵母(Saccharomycescerevisiae)相比,C.没有活性MTL等位基因的白色念珠菌纯合子不能交配,而不是作为细胞交配。纯合性与氟康唑耐药、交配与氟康唑耐药或转换与氟康唑耐药之间没有相关性,部分原因是大多数菌株在这种抗真菌剂广泛使用之前就已分离,只有3种菌株实际上具有耐药性。12个纯合子中有10个的核型重排,涉及4、5、6和7号染色体的一个或多个同源物。我们认为,核型重排,耐药性和纯合性来作为在感染过程中诱导超重组的结果,因此,它们往往一起发生,但每一个是同一事件的独立结果。此外,由于临床菌株可以交配并形成四倍体,交配和标记交换可能是C.体内白色念珠菌。
One hundred and twenty Candida albicans clinical isolates from the late 1980s and early 1990s were examined for homozygosity at the MTL locus. Of these, 108 were heterozygous (MTLa/MTLalpha), whereas seven were MTLa and five were MTLalpha. Five of the homozygous isolates were able to switch to the opaque cell morphology, while opaque cells were not detectable among the remaining seven. Nevertheless, all but one of the isolates homozygous at the MTL locus were shown to mate and to yield cells containing markers from both parents; the non-mater was found to have a frameshift in the MTLalpha1 gene. In contrast to Saccharomyces cerevisiae, C. albicans homozygotes with no active MTL allele failed to mate rather than mating as a cells. There was no correlation between homozygosity and fluconazole resistance, mating and fluconazole resistance or switching and fluconazole resistance, in part because most of the strains were isolated before the widespread use of this antifungal agent, and only three were in fact drug resistant. Ten of the 12 homozygotes had rearranged karyotypes involving one or more homologue of chromosomes 4, 5, 6 and 7. We suggest that karyotypic rearrangement, drug resistance and homozygosity come about as the result of induction of hyper-recombination during the infection process; hence, they tend to occur together, but each is the independent result of the same event. Furthermore, as clinical strains can mate and form tetraploids, mating and marker exchange are likely to be a significant part of the life cycle of C. albicans in vivo.