<title>Abstract</title><sec>
<title>Background</title>
<italic>Mycobacterium intracellulare</italic> is a representative etiological agent of emerging pulmonary <italic>M. avium-intracellulare</italic> complex disease in the industrialized countries worldwide. The recent genome sequencing of clinical strains isolated from pulmonary <italic>M. avium-intracellulare</italic> complex disease has provided insight into the genomic characteristics of pathogenic mycobacteria, especially for <italic>M. avium</italic>; however, the genomic characteristics of <italic>M. intracellulare</italic> remain to be elucidated.


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<title>Results</title>
In this study, we performed comparative genomic analysis of 55 <italic>M. intracellulare</italic> and related strains such as <italic>M. paraintracellulare</italic> (MP), <italic>M. indicus pranii</italic> (MIP) and <italic>M. yonogonense</italic>. Based on the average nucleotide identity, the clinical <italic>M. intracellulare</italic> strains were phylogenetically grouped in two clusters: (1) the typical <italic>M. intracellulare</italic> (TMI) group, including ATCC13950 and virulent M.i.27 and M.i.198 that we previously reported, and (2) the MP-MIP group. The alignment of the genomic regions was mostly preserved between groups. Plasmids were identified between groups and subgroups, including a plasmid common among some strains of the M.i.27 subgroup. Several genomic regions including those encoding factors involved in lipid metabolism (e.g., <italic>fadE3</italic>, <italic>fadE33</italic>), transporters (e.g., <italic>mce3</italic>), and type VII secretion system (genes of ESX-2 system) were shown to be hypermutated in the clinical strains. <italic>M. intracellulare</italic> was shown to be pan-genomic at the species and subspecies levels. The <italic>mce</italic> genes were specific to particular subspecies, suggesting that these genes may be helpful in discriminating virulence phenotypes between subspecies.


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<title>Conclusions</title>
Our data suggest that genomic diversity among <italic>M. intracellulare</italic>, <italic>M. paraintracellulare</italic>, <italic>M. indicus pranii</italic> and <italic>M. yonogonense</italic> remains at the subspecies or genovar levels and does not reach the species level. Genetic components such as <italic>mce</italic> genes revealed by the comparative genomic analysis could be the novel focus for further insight into the mechanism of human pathogenesis for <italic>M. intracellulare</italic> and related strains.


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