Comparative Genomic Analysis Reveals a Possible Novel Non-Tuberculous Mycobacterium Species with High Pathogenic Potential

Abstract

Mycobacteria have been reported to cause a wide range of human diseases. We present the first whole-genome study of a Non-Tuberculous Mycobacterium, Mycobacterium sp. UM_CSW (referred to hereafter as UM_CSW), isolated from a patient diagnosed with bronchiectasis. Our data suggest that this clinical isolate is likely a novel mycobacterial species, supported by clear evidence from molecular phylogenetic, comparative genomic, ANI and AAI analyses. UM_CSW is closely related to the Mycobacterium avium complex. While it has characteristic features of an environmental bacterium, it also shows a high pathogenic potential with the presence of a wide variety of putative genes related to bacterial virulence and shares very similar pathogenomic profiles with the known pathogenic mycobacterial species. Thus, we conclude that this possible novel Mycobacterium species should be tightly monitored for its possible causative role in human infections.

Fig 1. Circular representation of UM_CSW genome.

The indication for each feature from the outermost layer: (a) The alternating brown and yellow coloured bars represent the odd and even numbered contigs respectively; (b) The dark and light grey coloured bars represent the protein-coding genes in the forward and the reverse strands respectively; (c) rRNAs (light blue) and tRNAs (dark blue); (d) genomic islands (green); (e) virulence genes (red); (f) GC plot (purple and light green).

Fig 2. Phylogenetic relationship of UM_CSW with other mycobacterial species.

The phylogenetic tree was generated using core genome SNPs and the maximum likelihood method. Bootstrap numbers were generated in 1,000 runs. Nodes with bootstrap support values are indicated.

Fig 3. ANI analysis.

The top six relatives of Mycobacterium sp. UM_CSW are all members of the M. avium complex.

Fig 4. Functional classification of RAST-predicted protein-coding genes in the genome of UM_CSW.

Fig 5. Comparison of virulence genes in UM_CSW and other mycobacterial species.

Mycobacterium species were grouped according to their virulence gene profiles. From right to left: group 1, rapid growers M. chelonae to M. rhodesiae; group 2, members of the M. avium complex and UM_CSW; group 3, slow growers M. marinum, M. ulcerans and M. leprae and group 4, members of the M. tuberculosis complex.