CLONING, SEQUENCING, AND EXPRESSION OF THE MIG GENE OF MYCOBACTERIUM-AVIUM, WHICH CODES FOR A SECRETED MACROPHAGE-INDUCED PROTEIN

Mycobacterium avium is an intracellular pathogen that has evolved to b e a frequent cause of disseminated infection in immunocompromised pati ents. Although these bacilli are readily phagocytized, they are able t o survive and even multiply within human macrophages. The process wher eby mycobacteria circumvent the lytic functions of the macrophages is currently not well understood, but this is a key aspect in the pathoge nicity of all pathogenic mycobacteria. Previously, we identified a gen e in M. avium, designated mig (for macrophage-induced gene), the expre ssion of which is induced when the bacilli grow in human macrophages ( G. Plum and J. E. Clark-Curtiss, Infect. Immun. 62:476-483, 1994). In the present study we show that (i) the nucleotide sequence of the mig gene has an open reading frame of 295 amino acids with a strong bias f or mycobacterial codon usage, (ii) the mig gene also codes for a putat ive signal peptide of 19 amino acid residues, (iii) mig is induced by acidity to be expressed as an early-secreted 30-kDa protein, and (iv) the Mig protein exhibits an AMP-binding domain signature. However, bey ond this motif which is common to enzymes that activate a large variet y of substrates, no homologies to known sequences are found. We also s how that (v) Mycobacterium smegmatis strains expressing the Mig protei n have a limited advantage for survival in macrophages. These findings may be concordant with a role of the mig gene in the virulence of M. avium.