ADP-ribosylating and vacuolating cytotoxin of Mycoplasma pneumoniae represents unique virulence determinant among bacterial pathogens
ADP-ribosylating and vacuolating cytotoxin of Mycoplasma pneumoniae represents unique virulence determinant among bacterial pathogens
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DOI：
10.1073/pnas.0510644103
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发表时间：
2006-04-25
影响因子：
11.1
通讯作者：
Baseman, JB
中科院分区：
文献类型：
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作者：
Kannan, TR;Baseman, JB
与许多细菌性病原体不同，肺炎支原体并不会产生经典的毒素，而肺炎支原体究竟是如何损伤呼吸道上皮的，这在近50年来一直是个谜。在这里，我们报告了一种毒力因子（IMPN372）的鉴定，该毒力因子可能负责气道细胞损伤和与人类肺炎支原体感染相关的其他后遗症。我们发现肺炎支原体MPN372编码一个68 kda的蛋白，该蛋白具有adp -核糖基转移酶（ART）活性。在其N端，MPN372含有与NAD结合和adp核糖基化活性相关的关键氨基酸，类似于百日破毒素（PTX） S1亚基（PTX-S1）。有趣的是，与PTX-S1相比，MPN372 AIDP核糖化了相同和不同的哺乳动物蛋白。值得注意的是，MPN372引发了哺乳动物细胞的广泛空泡化和最终细胞死亡，包括器官培养中气管环中不同的和渐进的细胞病理学模式，这在以前被认为是由WT毒性肺炎支原体感染引起的。我们在诊断为肺炎支原体相关肺炎的患者中观察到显著的血清向MPN372的转化，表明这种毒素是在体内合成的，具有高度免疫原性的表位。
Unlike many bacterial pathogens, Mycoplasma pneumoniae is not known to produce classical toxins, and precisely how M. pneumoniae injures the respiratory epithelium has remained a mystery for > 50 years. Here, we report the identification of a virulence factor (IMPN372) possibly responsible for airway cellular damage and other sequelae associated with M. pneumoniae infections in humans. We show that M. pneumoniae MPN372 encodes a 68-kDa protein that possesses ADP-ribosyltransferase (ART) activity. Within its N terminus, MPN372 contains key amino acids associated with NAD binding and ADP-ribosylating activity, similar to pertussis toxin (PTX) S1 subunit (PTX-S1). Interestingly, MPN372 AIDP ribosylates both identical and distinct mammalian proteins when compared with PTX-S1. Remarkably, MPN372 elicits extensive vacuolization and ultimate cell death of mammalian cells, including distinct and progressive patterns of cytopathology in tracheal rings in organ culture that had been previously ascribed to infection with WT virulent M. pneumoniae. We observed dramatic seroconverSion to MPN372 in patients diagnosed with M. pneumoniae-associated pneumonia, indicating that this toxin is synthesized in vivo and possesses highly immunogenic epitopes.