“Mycobacterium indicus pranii” Is a Strain of Mycobacterium intracellulare

LETTER

In the recent publication “Comparative Analyses of Nonpathogenic, Opportunistic, and Totally Pathogenic Mycobacteria Reveal Genomic and Biochemical Variabilities and Highlight the Survival Attributes of Mycobacterium tuberculosis,” Rahman et al. (1) used bioinformatic methods to examine the evolutionary relatedness and metabolic capacity of mycobacteria of diverse pathogenic potential. A key conclusion of this work is the suggestion that “M. indicus pranii … is a predecessor of the M. avium complex and is at an evolutionarily transitory position with respect to a fast versus slow grower and as a saprophyte versus a seasoned pathogen.” In contrast, we suggest that this work provides strong evidence that “Mycobacterium indicus pranii” is a strain of Mycobacterium intracellulare.

The mycobacterial isolate currently known as “M. indicus pranii” was first described in the 1970s as “Mycobacterium w” and, due to some unusual immunomodulatory and biochemical properties, it has been proposed that this organism represents a distinct species (2). However, neither of its names is found on the List of Prokaryotic Names with Standing in Nomenclature, and the designation “Mycobacterium indicus pranii” does not conform to the binomial naming convention used for bacterial species (3).

Despite assertions that “M. indicus pranii” has a distinctive phenotypic profile, we are unaware of any studies that directly compare this organism with a comprehensive panel of M. intracellulare or Mycobacterium avium complex strains. In any case, many Mycobacterium spp. exhibit intraspecies diversity. M. avium encompasses environmental isolates and professional pathogens with diverse nutritional requirements and growth characteristics (4). Mycobacterium bovis is a facultative mammalian pathogen, whereas strains of M. bovis Bacille Calmette-Guérin (BCG) are used as vaccines against tuberculosis and immunotherapeutic agents for treatment of bladder cancer (5).

Because phenotypic results can be misleading, sequencing-based approaches are crucial to the accurate identification and designation of bacterial species. As Rahman et al. indicate, targeted sequencing of housekeeping genes (e.g., hsp70, gyrA, and dnaJ) reveals >99% sequence identity between “M. indicus pranii” and M. intracellulare, and their 16S rRNA sequences are identical. Contrary to the assertion by Rahman et al. that there are “notable differences in the 23S rRNA gene,” the entire rRNA operon of “M. indicus pranii” is identical to that of M. intracellulare MOTT-64 (GenBank accession no. NC_016948). Other strains of M. intracellulare do exhibit one to three changes in the 23S rRNA region, but these are heterogeneous, i.e., the polymorphisms in M. intracellulare ATCC 13950^T (GenBank accession no. NC_016946) are different from those in strain MOTT-36Y (GenBank accession no. NC_017904). No single rRNA polymorphism distinguishes “M. indicus pranii” from all strains of M. intracellulare.

Rahman et al. show that the homology of “M. indicus pranii” to M. intracellulare is not limited to the rRNA operon but extends to the entire genome. More than 4,900 (>95%) of the annotated protein coding genes from “M. indicus pranii” have homologs in M. intracellulare ATCC 13950^T (see Fig. 4 and supplemental Table S2 in reference 1). Although not explicitly discussed in this article, these genomes also show extensive synteny. An exception to this is an ~260-kb genomic inversion (kb 2708.9 to 2968.3 in the sequence deposited under GenBank accession no. NC_018612) that is specific to “M. indicus pranii.” As shown in Fig. 1 of this letter, the inversion encompasses genes MIP_03680 through MIP_04060, is flanked by a pair of transposons (MIP_03679 and MIP_04061), and disrupts two genes (MIP_03678 and MIP_04062) that have intact homologs in other M. avium complex genomes. As such, the proposed evolution of “M. indicus pranii” into a “predecessor of the M. avium complex” would have required a highly improbable series of events, including reversal of the inversion, loss of both transposons, and repair of the disrupted genes. In our view, it is more likely that the acquisition of the transposons and the inversion event are specific to the “M. indicus pranii” lineage of M. intracellulare and occurred long after the evolution of distinct M. avium complex species.

FIG 1 .

The genomic inversion present in “M. indicus pranii” (GenBank accession no. NC_018612) is absent from other M. avium complex organisms, including the sequenced genomes of M. intracellulare ATCC 13950^T (NC_016946), M. yongonense 05-1389 (NC_021715), and M. avium strains K10 (NC_002944) and 104 (NC_008595). Symbols: gray arrows, inverted regions; green rectangles, conserved flanking regions; blue and red arrows, flanking genes that are conserved and intact in most M. avium complex isolates but disrupted in “M. indicus pranii”; black arrows, transposons.

We understand that due to the therapeutic and commercial potential of “M. indicus pranii,” it may be desirable to differentiate this organism from other strains of M. intracellulare. Consistent with the approach used for M. bovis BCG, we suggest that “M. indicus pranii” be referred to as M. intracellulare MIP.