PARACOCCIDIOIDOMYCOSIS--EVOLUTION AND STRAIN-TYPING

我们的目标是研究巴西副球孢子菌的进化生物学，这是一种引起南美洲最重要的地方性真菌病--副球孢子菌病的子囊菌。我们的合作是哥伦比亚医学真菌学家和美国真菌学家之间的合作，前者具有巴西巴西里氏假丝酵母菌的临床和研究经验，后者具有真菌进化生物学的经验。我们有三个具体目标：(1)巴西巴氏原虫是一个物种还是多个物种？(2)巴西巴氏原虫是克隆性繁殖还是通过重组繁殖？(3)巴西巴氏原虫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)真菌物种的概念是形态的，但我们对组织胞浆菌、球孢子虫和黄曲霉的经验表明，一个形态物种可以包含一个以上的遗传隔离物种。这些物种可能有不同的表型，包括致病性，所以医生必须知道这些物种。我们将使用我们开发的与金龟子、黄曲霉和囊藻相同的策略，使用四到五个基因谱系的一致和不一致的界面来定义遗传隔离的物种。(2)巴西巴氏原虫被认为是克隆繁殖的，这意味着相同的致病基因可能会重复出现，并且任何可变的DNA区域都可以用来追踪菌株。然而，我们对金黄色葡萄球菌和黄曲霉的经验是，无性真菌也可以重组，导致不同的患者感染基因不同的病原体，而这些病原体不能只用一个基因来追踪。用于评估物种的相同数据也可以用于确定繁殖模式，同样是通过物种内的基因谱系一致性来确定。(3)如果临床分离株的基因类型不能代表所有环境分离株，比较两种类型分离株的基因组可能有助于寻找致病基因。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池可以解决这个问题。

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.