The role of Mycobacterium avium complex fibronectin attachment protein in adherence to the human respiratory mucosa

Mycobacterium avium complex (MAC) are opportunistic respiratory pathogens t hat infect non-immunocompromised patients with established lung disease, al though they can also cause primary infections. The ability to bind fibronec tin is conserved among many mycobacterial species. We have investigated the adherence of a sputum isolate of MAC to the mucosa of organ cultures const ructed with human tissue and the contribution of M. avium fibronectin attac hment protein (FAP) to the process. MAC adhered to fibrous, but not globula r mucus, and to extracellular matrix (ECM) in areas of epithelial damage, b ut 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 ga ve similar results. There was a significant reduction (P < 0.05) in the num ber of bacteria adhering to ECM after preincubation of bacteria with fibron ectin and after preincubation of the tissue with M. avium FAP in a concentr ation-dependant manner. The number of bacteria adhering to fibrous mucus wa s unchanged. Immunogold labelling demonstrated fibronectin in ECM as well a s in other areas of epithelial damage, but only ECM bound FAP. A Mycobacter ium 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 a reas of epithelial damage via FAP and to mucus with a fibrous appearance vi a another adhesin. Epithelial damage exposing ECM and poor mucus clearance will predispose to MAC airway infection.