Molecular genetic analyses of mating pheromones reveal intervariety mating or hybridization in Cryptococcus neoformans

Molecular genetic analyses of mating pheromones reveal intervariety mating or hybridization in Cryptococcus neoformans
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DOI:
10.1128/iai.70.9.5225-5235.2002
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发表时间:
2002-09-01
影响因子:
3.1
通讯作者:
Chaturvedi, S
Chaturvedi, S
中科院分区:
医学2区
文献类型:
--
作者:
Chaturvedi, V;Fan, JJ;Chaturvedi, S

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致病性酵母新隐球菌的性交配对致病机制的研究很重要,因为真菌的毒力与α交配型(MATalpha)有关。对122株新形假丝酵母的交配信息素(MFalpha1和MFalpha1)进行了分析,以了解品种间杂交或交配及其毒力。在三个新形态c . neformans变种中,MFalpha 1表现出(a)特定的核苷酸多态性,(b)不同的拷贝数和染色体定位,以及(c)在两个地理种群中独特的推断氨基酸。不同品种的MFalpha 1在南方杂交中交叉杂交。系统发育分析显示为净化选择(中性进化)。这些观察结果表明,来自三种新形式c的任何一种MATa菌株都可以与新形式c变种的MATa菌株进行自然交配或杂交。少数血清型A/D二倍体菌株提供了交配或杂交的证据,而大多数A/D菌株的单倍体MFalpha 1阳性与新形式C. var. grubii相同。二倍体的MFa1序列和拷贝数与格鲁比变种c.n oformans var. grubii相同,MFa1序列与格鲁比变种c.n oformans var. neoformans相同;因此,这些菌株是杂交的。小鼠生存曲线和组织学病变显示,A/D二倍体具有高致病性,其致病性水平与格鲁比变异型C. neoformans var. grubii型菌株相似,而与格鲁比变异型C. neoformans var. neoformans菌株的低致病性不同。与3个品种的mfapha 1相比,MFa1扩增子和杂交信号仅在2个新形态C. neoformans变种参考菌株和8个A/D二倍体中获得。这表明一种尚未被发现的MFa信息素在新生C. neformans var. gatii和新生C. neformans var. grubii中是不相关的,与新生C. neformans var. neformans高度分化的,或者比新生C. neformans var. neformans中更罕见。这些观察结果可以为今后研究异种交配在新形态线虫生物学和毒力中的作用奠定基础。
The sexual mating of the pathogenic yeast Cryptococcus neoformans is important for pathogenesis studies because the fungal virulence is linked to the alpha mating type (MATalpha). We characterized C. neoformans mating pheromones (MFalpha 1 and MFalpha1) from 122 strains to understand intervariety hybridization or mating and intervariety virulence. MFalpha 1 in three C. neoformans varieties showed (a) specific nucleotide polymorphisms, (b) different copy numbers and chromosomal localizations, and (c) unique deduced amino acids in two geographic populations of C. neoformans var. gattii. MFalpha 1 of different varieties cross-hybridized in Southern hybridizations. Their phylogenetic analyses showed purifying selection (neutral evolution). These observations suggested that MATalpha strains from any of the three C. neoformans varieties could mate or hybridize in nature with MATa strains of C. neoformans var. neoformans. A few serotype A/D diploid strains provided evidence for mating or hybridization, while a majority of A/D strains tested positive for haploid MFalpha 1 identical to that of C. neoformans var. grubii. MFalpha 1 sequence and copy numbers in diploids were identical to those of C. neoformans var. grubii, while their MFa1 sequences were identical to those of C. neoformans var. neoformans; thus, these strains were hybrids. The mice survival curves and histological lesions revealed A/D diploids to be highly pathogenic, with pathogenicity levels similar to that of the C. neoformans var. grubii type strain and unlike the low pathogenicity levels of C. neoformans var. neoformans strains. In contrast to MFalpha 1 in three varieties, MFa1 amplicons and hybridization signals could be obtained only from two C. neoformans var. neoformans reference strains and eight A/D diploids. This suggested that a yet undiscovered MFa pheromone (s) in C. neoformans var. gattii and C. neoformans var. grubii is unrelated to, highly divergent from, or rarer than that in C. neoformans var. neoformans. These observations could form the basis for future studies on the role of intervariety mating in C. neoformans biology and virulence.