The role of Mycobacterium avium complex fibronectin attachment protein in adherence to the human respiratory mucosa.
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.
Middleton
A M
AM
Imperial College of Science, Technology and Medicine at the National Heart and Lung Institute and Royal Brompton Hospital, Manresa Road, London SW3 6LR, UK.
Chadwick
M V
MV
Nicholson
A G
AG
Dewar
A
A
Groger
R K
RK
Brown
E J
EJ
Wilson
R
R
D000234:Adenoids / Q000382:microbiology / Q000473:pathology / Q000648:ultrastructure; D018829:Adhesins, Bacterial / Q000378:metabolism / Q000502:physiology*; D001980:Bronchi / Q000382:microbiology / Q000473:pathology / Q000648:ultrastructure; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D015269:Mycobacterium avium Complex; D009924:Organ Culture Techniques; D020545:Respiratory Mucosa / Q000382:microbiology* / Q000473:pathology / Q000648:ultrastructure; D012996:Solutions; D014420:Turbinates / Q000382:microbiology / Q000473:pathology / Q000648:ultrastructure
D018829:Adhesins, Bacterial; C117704:FAP-A protein, Mycobacterium avium; D005353:Fibronectins; D012996:Solutions