Characterization of the fibronectin-attachment protein of Mycobacterium avium reveals a fibronectin-binding motif conserved among mycobacteria.
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.
Schorey
J S
JS
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Holsti
M A
MA
Ratliff
T L
TL
Allen
P M
PM
Brown
E J
EJ
D017088:AIDS-Related Opportunistic Infections / Q000209:etiology; D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D003001:Cloning, Molecular; D017124:Conserved Sequence; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009161:Mycobacterium / Q000235:genetics* / Q000378:metabolism*; D015269:Mycobacterium avium Complex / Q000235:genetics* / Q000378:metabolism* / Q000472:pathogenicity; D015270:Mycobacterium avium-intracellulare Infection / Q000209:etiology; D009163:Mycobacterium bovis / Q000378:metabolism; D009842:Oligopeptides / Q000235:genetics* / Q000378:metabolism*; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
D005353:Fibronectins; D009842:Oligopeptides; C080493:fibronectin attachment peptide