Phenotypic and genomic analyses of the Mycobacterium avium complex reveal differences in gastrointestinal invasion and genomic composition

Mycobacterium avium and Mycobacterium intracellulare are closely related or ganisms and comprise the Mycobacterium avium complex. These organisms share many common characteristics, including the ability to cause life-threateni ng respiratory infections in people with underlying lung pathology or immun ological defects and occasionally in those with no known predisposing condi tions. However, the ability to invade the mucosa of the gastrointestinal tr act and cause disseminated disease in AIDS patients has not been epidemiolo gically linked to M. intracellulare and appears to be unique to M. avium. W e compared the abilities of M. avium and M. intracellulare to tolerate the acidic conditions of the stomach, to resist the membrane-disrupting activit y of cationic peptides, and to invade intestinal epithelial cells in vitro and in vivo. We observed that M. avium and M. intracellulare were both tole rant to the acidic conditions encountered in the stomach and resistant to c ationic peptides. However, when strains of M. avium and M. intracellulare w ere examined for their ability to enter cultured human intestinal cells or mouse intestinal mucosa, we observed that AL avium could invade more effici ently than M. intracellulare. To elucidate the basis of this pathogenic dif ference and identify genes involved in the invasion of the intestinal mucos a, we performed chromosomal DNA subtractive hybridization using M. avium an d M. intracellulare chromosomal DNAs. In all, 21 genes that were present in M. avium but absent in M. intracellulare were identified, including some t hat may be associated with the ability of M. avium to invade the intestinal mucosa.