The role of Mycobacterium avium complex fibronectin attachment protein in adherence to the human respiratory mucosa
The role of Mycobacterium avium complex fibronectin attachment protein in adherence to the human respiratory mucosa
复制标题
DOI：
10.1046/j.1365-2958.2000.02137.x
复制
发表时间：
2000-10-01
影响因子：
3.6
通讯作者：
Wilson, R
中科院分区：
文献类型：
--
作者：
Middleton, AM;Chadwick, MV;Wilson, R
鸟分枝杆菌复合体（MAC）是一种机会性呼吸道病原体，可感染已确诊肺部疾病的非免疫功能低下患者，尽管它们也可引起原发性感染。结合纤维连接蛋白的能力在许多分枝杆菌种类中是保守的。我们研究了MAC痰液分离物对人体组织构建的器官培养粘膜的粘附以及鸟分枝杆菌纤维连接蛋白（FAP）在这一过程中的作用。MAC粘附于纤维状黏液，但不粘附于球状黏液，以及上皮损伤区域的细胞外基质（ECM），但不粘附于完整的挤压细胞和胶原纤维。细菌偶尔会粘附在健康的非纤毛上皮和暴露其内容物的退化细胞上，但从不粘附在纤毛细胞上。不同呼吸组织的结果相似。两个ATCC菌株的MAC得到了相似的结果。细菌与纤维连接蛋白预孵育和组织与M. avium FAP预孵育后，ECM粘附的细菌数量均呈浓度依赖性降低（P < 0.05）。附着在纤维黏液上的细菌数量没有变化。免疫金标记显示纤维连接蛋白存在于ECM以及其他上皮损伤区域，但仅存在于ECM结合的FAP。耻垢分枝杆菌菌株对粘膜的粘附模式与MAC相同。当删除FAP基因时，菌株对ECM的粘附减少，当转染禽分枝杆菌FAP表达构建物时，菌株的粘附恢复。我们得出结论，MAC通过FAP粘附在上皮损伤区域的ECM上，并通过另一种粘附素粘附在具有纤维外观的粘液上。上皮损伤暴露出ECM和不良粘液清除将倾向于MAC气道感染。
Mycobacterium avium complex (MAC) are opportunistic respiratory pathogens that infect non-immunocompromised patients with established lung disease, although they can also cause primary infections. The ability to bind fibronectin is conserved among many mycobacterial species. We have investigated the adherence of a sputum isolate of MAC to the mucosa of organ cultures constructed with human tissue and the contribution of M. avium fibronectin attachment protein (FAP) to the process. MAC adhered to fibrous, but not globular mucus, and to extracellular matrix (ECM) in areas of epithelial damage, but not to intact extruded cells and collagen fibres. Bacteria occasionally adhered to healthy unciliated epithelium and to cells that had degenerated exposing their contents, but never to ciliated cells. The results obtained with different respiratory tissues were similar. Two ATCC strains of MAC gave similar results. There was a significant reduction (P < 0.05) in the number of bacteria adhering to ECM after preincubation of bacteria with fibronectin and after preincubation of the tissue with M. avium FAP in a concentration-dependant manner. The number of bacteria adhering to fibrous mucus was unchanged. Immunogold labelling demonstrated fibronectin in ECM as well as in other areas of epithelial damage, but only ECM bound FAP. A Mycobacterium smegmatis strain had the same pattern of adherence to the mucosa as MAC. When the FAP gene was deleted, the strain demonstrated reduced adherence to ECM, and adherence was restored when the strain was transfected with an M. avium FAP expression construct. We conclude that MAC adheres to ECM in areas of epithelial damage via FAP and to mucus with a fibrous appearance via another adhesin. Epithelial damage exposing ECM and poor mucus clearance will predispose to MAC airway infection.