Schorey J S, Holsti M A, Ratliff T L, Allen P M, Brown E J
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Mol Microbiol. 1996 Jul;21(2):321-9. doi: 10.1046/j.1365-2958.1996.6381353.x.
Mycobacterium avium is an intracellular pathogen and a major opportunistic infectious agent observed in patients with acquired immune deficiency syndrome (AIDS). Evidence suggests that the initial portal of infection by M. avium is often the gastrointestinal tract. However, the mechanism by which the M. avium crosses the epithelial barrier is unclear. A possible mechanism is suggested by the ability of M. avium to bind fibronectin, an extracellular matrix protein that is a virulence factor for several extracellular pathogenic bacteria which bind to mucosal surfaces. To further characterize fibronectin binding by M. avium, we have cloned the M. avium fibronectin-attachment protein (FAP). The M. avium FAP (FAP-A) has an unusually large number of Pro and Ala residues (40% overall) and is 50% identical to FAP of both Mycobacterium leprae and Mycobacterium tuberculosis. Using recombinant FAP-A and FAP-A peptides, we show that two non-continuous regions in FAP-A bind fibronectin. Peptides from these regions and homologous sequences from M. leprae FAP inhibit fibronectin binding by both M. avium and Mycobacterium bovis Bacillus Calmette-Guerin (BCG). These regions have no homology to eukaryotic fibronectin-binding proteins and are only distantly related to fibronectin-binding peptides of Gram-positive bacteria. Nevertheless, these fibronectin-binding regions are highly conserved among the mycobacterial FAPs, suggesting an essential function for this interaction in mycobacteria infection of their metazoan hosts.
鸟分枝杆菌是一种细胞内病原体，也是在获得性免疫缺陷综合征（AIDS）患者中观察到的主要机会性感染因子。有证据表明，鸟分枝杆菌的初始感染门户通常是胃肠道。然而，鸟分枝杆菌穿过上皮屏障的机制尚不清楚。鸟分枝杆菌结合纤连蛋白的能力提示了一种可能的机制，纤连蛋白是一种细胞外基质蛋白，是几种与粘膜表面结合的细胞外致病细菌的毒力因子。为了进一步表征鸟分枝杆菌与纤连蛋白的结合，我们克隆了鸟分枝杆菌纤连蛋白附着蛋白（FAP）。鸟分枝杆菌FAP（FAP-A）具有异常大量的脯氨酸和丙氨酸残基（总共40%），与麻风分枝杆菌和结核分枝杆菌的FAP有50%的同源性。使用重组FAP-A和FAP-A肽，我们表明FAP-A中的两个非连续区域结合纤连蛋白。来自这些区域的肽以及麻风分枝杆菌FAP的同源序列抑制鸟分枝杆菌和卡介苗（BCG）与纤连蛋白的结合。这些区域与真核纤连蛋白结合蛋白没有同源性，与革兰氏阳性细菌的纤连蛋白结合肽只有远缘关系。然而，这些纤连蛋白结合区域在分枝杆菌FAP中高度保守，表明这种相互作用在分枝杆菌感染后生动物宿主中具有重要功能。
