Eissenberg L G, Poirier S, Goldman W E
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Infect Immun. 1996 Dec;64(12):5310-4. doi: 10.1128/iai.64.12.5310-5314.1996.
Many Histoplasma capsulatum strains spontaneously give rise to variants during broth culture or subsequent to ingestion by epithelial cells. Unlike their parents, these variants are defective in killing macrophages and lack a major cell wall constituent, alpha-(1,3)-glucan. Inside macrophages, where the variants can persist for several weeks, they adopted an unusual morphology strikingly similar to that reported in the tissues of persistently infected humans or animals. These yeasts were often enlarged or misshapen (allomorphic), but were viable. Decreased cytotoxicity for macrophages was more strongly associated with allomorph formation than was the absence of cell wall alpha-(1,3)-glucan. Allomorphs were also formed in rat and mouse resident macrophages, but not in hamster trachea epithelial cells, indicating that host cell type influences the morphology of these yeasts. We propose that during H. capsulatum infection of mammalian hosts, spontaneous variants arise which can be recognized by their unusual morphologies. In contrast with their virulent parents, such variants "peacefully coexist" within macrophages, potentially contributing to the establishment of latency in vivo.
许多荚膜组织胞浆菌菌株在肉汤培养期间或被上皮细胞摄取后会自发产生变异体。与它们的亲本不同，这些变异体在杀死巨噬细胞方面存在缺陷，并且缺乏一种主要的细胞壁成分α-(1,3)-葡聚糖。在巨噬细胞内，变异体可以持续存在数周，它们呈现出一种异常的形态，与在持续感染的人类或动物组织中报道的形态惊人地相似。这些酵母细胞通常会增大或变形（异形），但仍具有活力。与缺乏细胞壁α-(1,3)-葡聚糖相比，对巨噬细胞细胞毒性的降低与异形形成的关联更为紧密。在大鼠和小鼠的驻留巨噬细胞中也会形成异形，但在仓鼠气管上皮细胞中则不会，这表明宿主细胞类型会影响这些酵母的形态。我们提出，在哺乳动物宿主受到荚膜组织胞浆菌感染期间，会出现自发变异体，其异常形态可被识别。与它们具有毒力的亲本不同，这些变异体在巨噬细胞内“和平共存”，可能有助于在体内建立潜伏感染。
