The white morphotype of Mycobacterium avium-intracellulare is common in infected humans and virulent in infection models

Isolates of Mycobacterium avium-intracellulare (MAI) form multiple colony t ypes named red-opaque, white-opaque, red-transparent (RT), and white-transp arent (WT). The newly discovered WT morphotype is multidrug resistant relat ive to other variants in vitro. To determine whether the WT morphotype occu rs in humans, 32 MAI-positive clinical samples from 2 sites were plated dir ectly onto indicator agar without prior passage in vitro. WT was the predom inant morphotype in 26 (81%) of these samples and was absent in only 2 samp les. WT variants grew better than isogenic RT variants in mouse and human m acrophage models of infection, and RT clones that passed through such syste ms underwent rapid shifts to the WT morphotype. The RT morphotype was heter ogeneous with regard to infectivity. In summary, the white morphotype was c ommon in humans and was favored in disease models. It may play an important role in the establishment and persistence of MAI infection.