Intracellular phenotype of Mycobacterium avium enters macrophages primarily by a macropinocytosis-like mechanism and survives in a compartment that differs from that with extracellular phenotype.

TitleIntracellular phenotype of Mycobacterium avium enters macrophages primarily by a macropinocytosis-like mechanism and survives in a compartment that differs from that with extracellular phenotype.
Publication TypeJournal Article
Year of Publication2004
AuthorsBermudez LE, Petrofsky M, Sangari F
JournalCell biology international
Volume28
Issue5
Pagination411-9
Date Published2004
ISSN1065-6995
KeywordsCell Compartmentation, Humans, Intracellular Space, Macrophages, Mycobacterium avium Complex, Mycobacterium avium-intracellulare Infection, Phenotype, Pinocytosis, Vacuoles
Abstract

Mycobacterium avium uptake by human macrophages differs between the phenotypes of bacterium grown in laboratory media (extracellular growth, EG) and bacterium grown within macrophages (intracellular growth, IG). Studies in vivo have confirmed that, when spreading, pathogenic mycobacteria enter macrophages by a complement receptor 3-independent pathway, in contrast to mycobacteria uptake in vitro. M. avium, grown in macrophages (IG) for 3 or more days, invade fresh macrophages by a macropinocytosis-like mechanism, in contrast to bacteria grown in media (EG), confirmed by the inhibitory effect of wortmannin, an inhibitor of phosphoinoside-3-kinase, on the uptake of IG, but not EG, by macrophages. The IG phenotype was seen in vacuoles with lower pH than those inhabited by the EG phenotype. Incubation of macrophages with bafilomycin A1, an inhibitor of vacuole acidification, decreased the viability of intracellular IG, but not EG, phenotype, suggesting the importance of an acidic environment for the regulation of IG genes. In addition, the percentage of vacuoles that incorporate and retain LAMP-1 is smaller with EG than with IG bacteria. The formation of M. avium macropinosomes was also shown to be independent of microtubules. These data suggest that uptake of extracellular fluid is part of M. avium IG phenotype uptake by macrophages, and that the IG phenotype inhabits a slightly different vacuole than that of EG.

Alternate JournalCell Biol. Int.