Characterisation, discrimination and phylogenetic study of clinically significant members of the Mycobacterium abscessus/chelonae taxonomic complex

Abstract

Rapidly growing mycobacteria are rare in clinical samples or as significant human pathogens. Members of the Mycobacterium abscessus/chalone complex are notable exceptions, implicated as colonisers and potential pathogens in a variety of clinical situations. Cystic fibrosis patients, with reduced lung function, can be colonised with organisms from this complex. An apparent poorer prognosis, post lung transplant, associated with Mycobacterium abscessus colonisation, potentially precluding lung transplantation, complicates this. At the start of this project reliable discrimination between these species was problematic. Given the clinical importance this project sought to compare the genomes of M. abscessus and M. chelonae, improve identification and explain differences in pathogenicity. Initially there were many whole genomes for Mycobacterium abscessus but none for Mycobacterium chelonae so a whole genome sequence for a clinical strain confidently assigned as M. chelonae (HPA 006) was obtained using the Ion Torrent (IT) and MinION (ONT) platforms. These data were used to identify regions of difference between these two species for identification and to explain putative variations in virulence and antibiotic resistance. Average Nucleotide Analysis (ANI) confirmed Mycobacterium abscessus and Mycobacterium chelonae complex as separate species. A pangenome study using PPanGGOLiN identified 655 genes present in M. abscessus (ATCC 19977) but absent from M. chelonae strains. AntiSMASH analysis highlighted differences in the overall number of Biosynthetic Gene Clusters (BGC) present in each species and identified BGCs present in one species but absent in the other. Of the 655 differential genes identified the largest category was hypothetical, including proteins with domains of unknown function. Despite annotation other genes proved challenging to correlate with known mechanisms of resistance or virulence. There were many genomic elements, present in both M. chelonae HPA 006 and M. abscessus (ATCC 19977), which show more difference in sequence than average. These differences, suggesting selection and a modified function, may account for the difference in virulence between the strains.