Abstract
Mycobacterium avium complex (MAC) infection causes disseminated disease in immunocompromised hosts, such as human immunodeficiency virus (HIV)-positive patients, and pulmonary disease in persons without systemic immunosuppression, which has been increasing in many countries. In Japan, the incidence of pulmonary MAC disease caused by M. avium is about 7 times higher than that caused by M. intracellulare. To explore the bacterial factors that affect the pathological state of MAC disease caused by M. avium, we determined the complete genome sequence of the previously unreported M. avium subsp. hominissuis strain TH135 isolated from a HIV-negative patient with pulmonary MAC disease and compared it with the known genomic sequence of M. avium strain 104 derived from an acquired immunodeficiency syndrome patient with MAC disease. The genome of strain TH135 consists of a 4,951,217-bp circular chromosome with 4,636 coding sequences. Comparative analysis revealed that 4,012 genes are shared between the two strains, and strains TH135 and 104 have 624 and 1,108 unique genes, respectively. Many strain-specific regions including virulence-associated genes were found in genomes of both strains, and except for some regions, the G+C content in the specific regions was low compared with the mean G+C content of the corresponding chromosome. Screening of clinical isolates for genes located in the strain-specific regions revealed that the detection rates of strain TH135-specific genes were relatively high in specimens isolated from pulmonary MAC disease patients, while, those of strain 104-specific genes were relatively high in those from HIV-positive patients. Collectively, M. avium strains that cause pulmonary and disseminated disease possess genetically distinct features, and it suggests that the acquisition of specific genes during strain evolution has played an important role in the pathological manifestations of MAC disease.
Highlights
Many species of nontuberculous mycobacteria (NTM) are found in a variety of habitats, including natural water, water distribution systems, bathrooms, soil, and household dust [1,2,3,4]
General Genomic Features To explore the bacterial factors that affect the establishment of pulmonary disease caused by M. avium subsp. hominissuis, we determined the whole genome sequence of the previously unreported M. avium strain TH135 isolated from a human immunodeficiency virus (HIV)-negative patient with pulmonary disease and compared it with the complete genome of M. avium strain 104 derived from an acquired immunodeficiency syndrome (AIDS) patient with Mycobacterium avium complex (MAC) disease [27]
The replication origin of the strain TH135 chromosome was deduced on the basis of the transition point in GC skew analysis and the presence of the dnaA gene accompanied by several DnaA boxes (Fig. 1)
Summary
Many species of nontuberculous mycobacteria (NTM) are found in a variety of habitats, including natural water, water distribution systems, bathrooms, soil, and household dust [1,2,3,4]. The clinical isolates used in this study comprised 35 M. avium strains including the genome analysis strain TH135 recovered from the sputa of HIV-negative patients with pulmonary MAC disease at the National Hospital Organization, Higashinagoya National Hospital in Japan from 2004 to 2008. General Genomic Features To explore the bacterial factors that affect the establishment of pulmonary disease caused by M. avium subsp.
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