Genomic Comparisons Reveal Microevolutionary Differences in Mycobacterium abscessus Subspecies

Abstract

Mycobacterium abscessus, a rapid-growing non-tuberculous mycobacterium, has been the cause of sporadic and outbreak infections world-wide. The subspecies in M. abscessus complex (M. abscessus, M. massiliense, and M. bolletii) are associated with different biologic and pathogenic characteristics and are known to be among the most frequently isolated opportunistic pathogens from clinical material. To date, the evolutionary forces that could have contributed to these biological and clinical differences are still unclear. We compared genome data from 243 M. abscessus strains downloaded from the NCBI ftp Refseq database to understand how the microevolutionary processes of homologous recombination and positive selection influenced the diversification of the M. abscessus complex at the subspecies level. The three subspecies are clearly separated in the Minimum Spanning Tree. Their MUMi-based genomic distances support the separation of M. massiliense and M. bolletii into two subspecies. Maximum Likelihood analysis through dN/dS (the ratio of number of non-synonymous substitutions per non-synonymous site, to the number of synonymous substitutions per synonymous site) identified distinct genes in each subspecies that could have been affected by positive selection during evolution. The results of genome-wide alignment based on concatenated locally-collinear blocks suggest that (a) recombination has affected the M. abscessus complex more than mutation and positive selection; (b) recombination occurred more frequently in M. massiliense than in the other two subspecies; and (c) the recombined segments in the three subspecies have come from different intra-species and inter-species origins. The results lead to the identification of possible gene sets that could have been responsible for the subspecies-specific features and suggest independent evolution among the three subspecies, with recombination playing a more significant role than positive selection in the diversification among members in this complex.

Subspecies-specific sequence detection for differentiation of Mycobacterium abscessus complex

“…We suspect that it is a result of the horizontal gene transfer between bacteria within the complex. This phenomenon was suggested as an important factor contributing to the evolution of M. abscessus 26,27 . M. abscessus is considered a pathogen with open, non-conservative pangenome, which means it should be monitored closely for the acquisition of pathogenic traits 28 .…”

“…Tan et al found that recombination MABC more than mutations and natural selection. After a comparison of 243 genomes of M. abscessus, they found that the recombined sequences in the three subspecies have come from different intra-species and inter-species origins 27 . The observations of Tan et al reflected in our study.…”

“…There are reports that recombination occurs more frequently in M. abscessus subsp. massiliense than in the other two subspecies 27 , which can explain why two subspecies specific sequences are necessary to discriminate M. abscessus subsp efficiently. massiliense from other members of the complex.…”

Mycobacterial genomics and structural bioinformatics: opportunities and challenges in drug discovery

“…In the case of M. abscessus , phylogenomic studies revealed the major role of recombination in causing lineage diversity [30,38,39]. Population structure and recombination analyses provided significant evidence of gene flow and admixture among three lineages ( M. abscessus , M. massiliense , and M. bolleti ), and a correlation with pathogenicity and macrolide resistance in cystic fibrosis patients was found [39].…”

Mycobacterium abscessus: Shapeshifter of the Mycobacterial World

“…In recent years, MABS has been further characterized into three distinct subspecies; MABS subspecies abscessus , MABS subspecies bolletii and MABS subspecies massiliense ( Adekambi et al, 2017 ). They differ in terms of drug susceptibility, and may have differences related to transmissibility as well which will be discussed ( Tan et al, 2017 ). Genomic analysis of MABS reveals evidence of horizontal gene transfer ( Howard et al, 2002 ).…”