PARACOCCIDIOIDOMYCOSIS--EVOLUTION AND STRAIN-TYPING

我们的目的是研究巴西副球孢子菌（paracoccidiides brasiliensis）的进化生物学，这是一种引起南美最重要的地方性真菌病副球孢子菌病的子囊真菌。我们的研究是哥伦比亚医学真菌学家与具有巴西疟原虫临床和研究经验的医学真菌学家与具有真菌进化生物学经验的美国真菌学家之间的合作。我们有三个具体目标：(1)巴西疟原虫是一个物种还是多个物种？(2)巴西螺是通过无性繁殖还是重组繁殖？(3)巴西疟原虫的临床分离株是环境分离株的代表，还是只有一些环境基因型能够感染人类？每个目标的重要性和方法如下。(1)真菌的物种概念是形态学的，但我们对荚膜组织原体、免疫球虫和黄曲霉的研究表明，一个形态学的物种可以包含多个遗传分离的物种。这些物种可能有不同的表型，包括致病性，所以医生必须了解这些物种。我们将使用与C. immitis， A. flavus和H. capsulatum相同的策略，利用四或五个基因谱系的一致性和不一致性界面来定义遗传分离的物种。(2) brasiliensis被认为是无性繁殖的，这意味着相同的致病基因型可能会反复遇到，并且任何可变的DNA区域都可以用来追踪菌株。然而，我们对C. immitis和A. flavus的经验是无性真菌也可以重组；导致不同的病人感染了基因上不同的病原体，而这些病原体无法用一个基因来追踪。用来评估物种的相同数据也可以用来确定繁殖模式，同样是通过物种内基因谱系的一致性。(3)如果临床分离株的基因型不能代表所有环境分离株，那么比较两种分离株的基因组可能有助于找到致病基因。寻找致病基因是医学真菌学领域的目标之一，比较病原体和非病原体的DNA库可以解决这个问题。

We aim to study the evolutionary biology of Paracoccidioides brasiliensis, the ascomycete fungus that causes paracoccidioidomycosis, the most important endemic mycosis in South America. Ours is a collaboration between Colombian medical mycologists with clinical and research experience with P. brasiliensis and a US mycologist experienced with fungal evolutionary biology. We have three specific aims: (1) Is P. brasiliensis one species or more than one? (2) Does P. brasiliensis reproduce clonally or by recombination? (3) Are clinical isolates of P. brasiliensis representative of environmental isolates, or are only some environmental genotypes capable of infecting humans? The importance and approach for each aim follow. (1) Fungal species concepts are morphological, but our experience with Histoplasma capsulatum, Coccidioides immitis and Aspergillus flavus shows that a morphological species can harbor more than one genetically isolated species. These species may have different phenotypes, including pathogenicity, so physicians must know the species. We will use the same strategy that we developed with C. immitis, A. flavus and H. capsulatum to use the interface of congruence and incongruity of four or five gene genealogies to define genetically isolated species. (2) P. brasiliensis is thought to reproduce clonally, which means that the same pathogenic genotype may be encountered repeatedly and that any variable DNA region could be used to track strains. However, our experience with C. immitis and A. flavus is that asexual fungi can also recombine; causing different patients to be infected with genetically different pathogens which cannot be tracked with just one gene. The same data used to assess species can be used to determine reproductive mode, again by gene genealogy congruence within species. (3) If genotypes of clinical isolates are not representative of all environmental isolates, it is possible that comparison of the genomes of the two types of isolates may help find genes responsible for pathogenicity. Finding pathogenicity genes is one of the goals of the field of medical mycology and comparing pools of DNA from pathogens and nonpathogens could solve the problem.