PARACOCCIDIOIDOMYCOSIS--EVOLUTION AND STRAIN-TYPING

我们的目的是研究巴西副球孢子菌的进化生物学，副球孢子菌病是南美洲最重要的地方性真菌病。 我们的合作是哥伦比亚医学真菌学家与具有巴西假单胞菌临床和研究经验的美国真菌学家在真菌进化生物学方面的合作。 我们有三个具体的目标：（1）是一个物种，还是一个以上的？(2)巴西对虾是无性繁殖还是重组繁殖？(3)巴西青霉临床分离株是否代表环境分离株，或者仅某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学的，但我们的经验与组织胞浆菌，粗球孢子菌和黄曲霉表明，形态物种可以窝藏一个以上的遗传隔离的物种。 这些物种可能具有不同的表型，包括致病性，因此医生必须了解该物种。 我们将使用与C开发的相同的策略。immitis、艾美耳球虫A. flavus和H. capsulatum使用四个或五个基因谱系的一致性和不一致性的界面来定义遗传隔离的物种。(2)巴西青霉被认为是克隆繁殖的，这意味着相同的致病基因型可能会重复出现，任何可变的DNA区域都可以用来追踪菌株。 然而，我们的经验与C。immitis和A.黄之处在于，无性真菌也可以重组;导致不同的患者感染遗传上不同的病原体，而这些病原体无法仅用一个基因进行追踪。 用于评估物种的相同数据可用于确定繁殖模式，同样是通过物种内的基因谱系一致性。(3)如果临床分离株的基因型不能代表所有的环境分离株，那么比较两种类型分离株的基因组可能有助于找到致病性基因。 寻找致病基因是医学真菌学的目标之一，比较病原菌和非病原菌的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.