Identification of a beta 1 integrin on Mycobacterium avium-Mycobacterium intracellulare.
Mycobacterium avium-Mycobacterium intracellulare (MAI) is an opportunistic intracellular pathogen responsible for the highest incidence of disseminated bacterial infection in patients with AIDS. Treatment of the infection is extremely difficult and has shown limited efficacy. A critical event in the initiation of a variety of bacterial infections involves the adherence of bacteria to host cell surfaces. In the present study, we have shown that MAI organisms bind avidly to extracellular matrix proteins such as laminin, collagen I, and fibronectin in an in vitro attachment assay. Immunoblot analysis of a sonicate of MAI with polyclonal antibodies against different integrin receptors indicated that the sonicate cross-reacts with polyclonal antibodies against a human laminin-binding integrin, alpha 3 beta 1, and a human fibronectin-binding integrin, alpha 5 beta 1, although it is reactive with only the beta 1 subunit in the case of both antisera. Antibodies against the alpha 3 beta 1 and alpha 5 beta 1 integrins specifically inhibited the binding of MAI to laminin, collagen I, and fibronectin by 70 to 97%, depending on the ligand, suggesting that the attachment of MAI to these extracellular matrix proteins may be mediated by a beta 1 integrin. Furthermore, the attachment of MAI to laminin, collagen I, and fibronectin was found to be cation dependent. MAI may use this and other beta 1-containing integrins to adhere and penetrate through basement membrane structures that underlie host cell linings. An understanding of the mechanism of attachment and a definition of the adhesive molecules on the surface of MAI may open up new approaches to the prevention of serious infection caused by this organism.
Rao
S P
SP
Department of Medicine, Pulmonary, University of California, San Diego 92103-8374.
Gehlsen
K R
KR
Catanzaro
A
A
D001422:Bacterial Adhesion; D003429:Cross Reactions; D004492:Edetic Acid / Q000494:pharmacology; D019012:Integrin beta1; D016023:Integrins / Q000302:isolation & purification / Q000502:physiology*; D015269:Mycobacterium avium Complex / Q000502:physiology*; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic / Q000502:physiology; D017474:Receptors, Laminin
D019012:Integrin beta1; D016023:Integrins; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic; D017474:Receptors, Laminin; D004492:Edetic Acid