Genetic Involvement of Mycobacterium avium Complex in the Regulation and Manipulation of Innate Immune Functions of Host Cells.

Mycobacterium avium complex (MAC), a collection of mycobacterial species representing nontuberculous mycobacteria, are characterized as ubiquitous and opportunistic pathogens. The incidence and prevalence of infectious diseases caused by MAC have been emerging globally due to complications in the treatment of MAC-pulmonary disease (PD) in humans and the lack of understating individual differences in genetic traits and pathogenesis of MAC species or subspecies. Despite genetically close one to another, mycobacteria species belonging to the MAC cause diseases to different host range along with a distinct spectrum of disease. In addition, unlike Mycobacterium tuberculosis, the underlying mechanisms for the pathogenesis of MAC infection from environmental sources of infection to their survival strategies within host cells have not been fully elucidated. In this review, we highlight unique genetic and genotypic differences in MAC species and the virulence factors conferring the ability to MAC for the tactics evading innate immune attacks of host cells based on the recent advances in genetic analysis by exemplifying M. avium subsp. hominissuis, a major representative pathogen causing MAC-PD in humans. Further understanding of the genetic link between host and MAC may contribute to enhance host anti-MAC immunity, but also provide novel therapeutic approaches targeting the pangenesis-associated genes of MAC.

Genetic diversity and phylogeny of Mycobacterium avium.

Mycobacterium avium, one of the species of the M. avium complex (MAC), includes 4 subspecies, i.e., M. avium subsp. hominissuis (MAH), M. avium subsp. avium (MAA), M. avium subsp. silvaticum (MAS) and M. avium subsp. paratuberculosis (MAP), in turn classified into the S (sheep) and C (cattle) types. These subspecies, although closely related, represent distinct organisms, each endowed with specific pathogenetic and host range characteristics, ranging from environmental opportunistic bacteria that cause infections in swine and immunocompromised patients to pathogens of birds and ruminants. The present review summarizes the basic epidemiological and pathological features of the M. avium subspecies, describes the major genomic events responsible of M. avium subspecies diversity (insertion sequences, sequence variations in specific chromosome loci or genes, deletions, duplications and insertions of large genomic regions) and then reconstructs the phylogenetic relationships among the M. avium subspecies.

Hypersensitivity pneumonitis caused by Mycobacterium avium subsp. hominissuis in a hot tub, as proven by IS1245 RFLP and rep-PCR typing.

A symptomatic patient had repeatedly positive cultures of Mycobacterium avium subsp. hominissuis after exposure to a hot tub contaminated with M. avium subsp. hominissuis. The pulmonary and tub water isolates were indistinguishable by IS1245 RFLP as well as rep-PCR typing. Discontinued use of the hot tub resulted in culture conversion.