Pneumocystis, a major opportunistic pathogen in patients with a broad range of immunodeficiencies, contains abundant surface proteins encoded by a multicopy gene family, termed the major surface glycoprotein (Msg) gene superfamily. This superfamily has been identified in all Pneumocystis species characterized to date, highlighting its important role in Pneumocystis biology. In this report, through a comprehensive and in-depth characterization of 459 msg genes from 7 Pneumocystis species, we demonstrate, for the first time, the phylogeny and evolution of conserved domains in Msg proteins and provide a detailed description of the classification, unique characteristics, and phylogenetic relatedness of five Msg families. We further describe, for the first time, the relative expression levels of individual msg families in two rodent Pneumocystis species, the substantial variability of the msg repertoires in P. carinii from laboratory and wild rats, and the distinct features of the expression site for the classic msg genes in Pneumocystis from 8 mammalian host species. Our analysis suggests multiple functions for this superfamily rather than just conferring antigenic variation to allow immune evasion as previously believed. This study provides a rich source of information that lays the foundation for the continued experimental exploration of the functions of the Msg superfamily in Pneumocystis biology.IMPORTANCE Pneumocystis continues to be a major cause of disease in humans with immunodeficiency, especially those with HIV/AIDS and organ transplants, and is being seen with increasing frequency worldwide in patients treated with immunodepleting monoclonal antibodies. Annual health care associated with Pneumocystis pneumonia costs ∼$475 million dollars in the United States alone. In addition to causing overt disease in immunodeficient individuals, Pneumocystis can cause subclinical infection or colonization in healthy individuals, which may play an important role in species preservation and disease transmission. Our work sheds new light on the diversity and complexity of the msg superfamily and strongly suggests that the versatility of this superfamily reflects multiple functions, including antigenic variation to allow immune evasion and optimal adaptation to host environmental conditions to promote efficient infection and transmission. These findings are essential to consider in developing new diagnostic and therapeutic strategies.

中文翻译：

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多种肺孢子虫压缩基因组中大表面蛋白家族的多样性和复杂性。

肺孢子菌是广泛免疫缺陷患者的主要机会性病原体，含有丰富的由多拷贝基因家族编码的表面蛋白，称为主要表面糖蛋白 (Msg) 基因超家族。这个超家族已经在迄今为止表征的所有肺孢子虫物种中被鉴定出来，突出了它在肺孢子虫生物学中的重要作用。在本报告中，通过对来自 7 个肺孢子虫属物种的 459 个 msg 基因进行全面深入的表征，我们首次展示了 Msg 蛋白中保守结构域的系统发育和进化，并提供了分类、独特特征的详细描述，以及五个 Msg 家族的系统发育相关性。我们第一次进一步描述，两种啮齿类肺孢子虫中单个味精家族的相对表达水平，实验室和野生大鼠卡氏肺孢子虫中味精库的显着变异性，以及来自 8 个哺乳动物宿主的肺孢子虫中经典味精基因表达位点的独特特征物种。我们的分析表明该超家族具有多种功能，而不是像以前认为的那样仅仅赋予抗原变异以允许免疫逃避。这项研究提供了丰富的信息来源，为继续实验探索 Msg 超家族在肺孢子菌生物学中的功能奠定了基础。重要性肺孢子菌仍然是人类免疫缺陷疾病的主要原因，尤其是艾滋病毒/艾滋病和艾滋病毒感染者。器官移植，并且在世界范围内用免疫耗竭性单克隆抗体治疗的患者中出现的频率越来越高。仅在美国，与肺​​孢子菌肺炎相关的年度医疗保健费用就高达 4.75 亿美元。除了在免疫缺陷个体中引起明显疾病外，肺孢子菌还可在健康个体中引起亚临床感染或定植，这可能在物种保存和疾病传播中起重要作用。我们的工作揭示了味精超家族的多样性和复杂性，并强烈表明该超家族的多功能性反映了多种功能，包括允许免疫逃避的抗原变异和对宿主环境条件的最佳适应，以促进有效的感染和传播。