Chang Y C, Penoyer L A, Kwon-Chung K J
Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3258-63. doi: 10.1073/pnas.061031998. Epub 2001 Feb 27.
Cryptococcus neoformans STE12alpha, a homologue of Saccharomyces cerevisiae STE12, exists only in MATalpha strains. We identified another STE12 homologue, STE12a, which is MATa specific. As in the case with Deltaste12alpha, the mating efficiency for Deltaste12a was reduced significantly. The Deltaste12a strains surprisingly still mated with Deltaste12alpha strains. In MATalpha strains, STE12a functionally complemented STE12alpha for mating efficacy, haploid fruiting, and regulation of capsule size in the mouse brain. Furthermore, when STE12a was replaced with two copies of STE12alpha, the resulting MATa strain produced hyphae on filament agar. STE12a regulates mRNA levels of several genes that are important for virulence including CNLAC1 and CAP genes. STE12a also modulates enzyme activities of phospholipase and superoxide dismutase. Importantly, deletion of STE12a markedly reduced the virulence in mice, as is the case with STE12alpha. Brain smears of mice infected with the Deltaste12a strain showed yeast cells with a considerable reduction in capsule size compared with those infected with STE12a strains. When the disrupted locus of ste12a was replaced with a wild-type STE12a gene, both in vivo and in vitro mutant phenotypes were reversed. These results suggest that STE12a and STE12alpha have similar functions, and that the mating type of the cells influences the alleles to exert their biological effects. C. neoformans, thus, is the first fungal species that contains a mating-type-specific STE12 homologue in each mating type. Our results demonstrate that mating-type-specific genes are not only important for saprobic reproduction but also play an important role for survival of the organism in host tissue.
新型隐球菌STE12α是酿酒酵母STE12的同源物，仅存在于MATα菌株中。我们鉴定出了另一个STE12同源物STE12a，它是MATa特异性的。与Δste12α的情况一样，Δste12a的交配效率显著降低。令人惊讶的是，Δste12a菌株仍能与Δste12α菌株交配。在MATα菌株中，STE12a在交配效力、单倍体产孢以及小鼠脑中荚膜大小的调节方面对STE12α起到功能互补作用。此外，当STE12a被两个拷贝的STE12α取代时，所得的MATa菌株在丝状琼脂上产生了菌丝。STE12a调节几个对毒力很重要的基因的mRNA水平，包括CNLAC1和CAP基因。STE12a还调节磷脂酶和超氧化物歧化酶的酶活性。重要的是，删除STE12a会显著降低小鼠的毒力，与STE12α的情况相同。感染Δste12a菌株的小鼠脑涂片显示，与感染STE12a菌株的小鼠相比，酵母细胞的荚膜大小显著减小。当ste12a的破坏位点被野生型STE12a基因取代时，体内和体外的突变表型都得到了逆转。这些结果表明，STE12a和STE12α具有相似的功能，并且细胞的交配型会影响等位基因发挥其生物学效应。因此，新型隐球菌是第一个在每个交配型中都含有交配型特异性STE12同源物的真菌物种。我们的结果表明，交配型特异性基因不仅对腐生繁殖很重要，而且对生物体在宿主组织中的存活也起着重要作用。
