Middleton A M, Chadwick M V, Nicholson A G, Dewar A, Groger R K, Brown E J, Wilson R
Imperial College of Science, Technology and Medicine at the National Heart and Lung Institute and Royal Brompton Hospital, Manresa Road, London SW3 6LR, UK.
Mol Microbiol. 2000 Oct;38(2):381-91. doi: 10.1046/j.1365-2958.2000.02137.x.
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.
鸟分枝杆菌复合群（MAC）是机会性呼吸道病原体，可感染患有既定肺部疾病的非免疫受损患者，尽管它们也可引起原发性感染。许多分枝杆菌物种都具有结合纤连蛋白的能力。我们研究了一株MAC痰液分离株对用人组织构建的器官培养物黏膜的黏附情况，以及鸟分枝杆菌纤连蛋白附着蛋白（FAP）在这一过程中的作用。MAC黏附于纤维状而非球状黏液，以及上皮损伤区域的细胞外基质（ECM），但不黏附于完整的挤出细胞和胶原纤维。细菌偶尔会黏附于健康的无纤毛上皮细胞以及内容物已暴露的变性细胞，但从不黏附于纤毛细胞。不同呼吸道组织获得的结果相似。两株MAC ATCC菌株也得到了类似结果。在用纤连蛋白预孵育细菌以及用不同浓度的鸟分枝杆菌FAP预孵育组织后，黏附于ECM的细菌数量显著减少（P<0.05）。黏附于纤维状黏液的细菌数量没有变化。免疫金标记显示ECM以及上皮损伤的其他区域存在纤连蛋白，但只有ECM结合FAP。耻垢分枝杆菌菌株与MAC对黏膜的黏附模式相同。当FAP基因缺失时，该菌株对ECM的黏附减少，而当用鸟分枝杆菌FAP表达构建体转染该菌株时，黏附得以恢复。我们得出结论，MAC通过FAP黏附于上皮损伤区域的ECM，并通过另一种黏附素黏附于外观呈纤维状的黏液。上皮损伤导致ECM暴露以及黏液清除不良会增加MAC气道感染的易感性。
