Cacalano G, Kays M, Saiman L, Prince A
Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York 10032.
J Clin Invest. 1992 Jun;89(6):1866-74. doi: 10.1172/JCI115791.
The pathogenesis of Pseudomonas aeruginosa infection in cystic fibrosis (CF) is a complex process attributed to specific characteristics of both the host and the infecting organism. In this study, the properties of the PAO1 neuraminidase were examined to determine its potential role in facilitating Pseudomonas colonization of the respiratory epithelium. The PAO1 neuraminidase was 1000-fold more active than the Clostridium perfringens enzyme in releasing sialic acid from respiratory epithelial cells. This effect correlated with increased adherence of PAO1 to epithelial cells after exposure to PAO1 neuraminidase and was consistent with in vitro studies demonstrating Pseudomonas adherence to asialoganglioside receptors. The regulation of the neuraminidase gene nanA was examined in Pseudomonas and as cloned and expressed in Escherichia coli. In hyperosmolar conditions neuraminidase expression was increased by 50% (P less than 0.0004), an effect which was OmpR dependent in E. coli. In Pseudomonas the osmotic regulation of neuraminidase production was dependent upon algR1 and algR2, genes involved in the transcriptional activation of algD, which is responsible for the mucoid phenotype of Pseudomonas and pathognomonic for chronic infection in CF. Under the hyperosmolar conditions postulated to exist in the CF lung, nanA is likely to be expressed to facilitate the initial adherence of Pseudomonas to the respiratory tract.
囊性纤维化(CF)中铜绿假单胞菌感染的发病机制是一个复杂的过程,这归因于宿主和感染生物体的特定特征。在本研究中,对PAO1神经氨酸酶的特性进行了检测,以确定其在促进假单胞菌在呼吸道上皮定植中的潜在作用。PAO1神经氨酸酶从呼吸道上皮细胞释放唾液酸的活性比产气荚膜梭菌酶高1000倍。这种效应与暴露于PAO1神经氨酸酶后PAO1对上皮细胞粘附增加相关,并且与体外研究显示假单胞菌对去唾液酸神经节苷脂受体的粘附一致。在假单胞菌中检测了神经氨酸酶基因nanA的调控,并在大肠杆菌中进行克隆和表达。在高渗条件下,神经氨酸酶表达增加了50%(P小于0.0004),在大肠杆菌中这种效应依赖于OmpR。在假单胞菌中,神经氨酸酶产生的渗透调节依赖于algR1和algR2,这两个基因参与algD的转录激活,algD负责假单胞菌的粘液样表型,是CF慢性感染的特征性表现。在假定存在于CF肺中的高渗条件下,nanA可能会表达以促进假单胞菌对呼吸道上皮的初始粘附。