Genome reorganization during emergence of host-associated Mycobacterium abscessus

Abstract

Mycobacterium abscessus is a rapid growing, free-living species of bacterium that also causes lung infections in humans. Human infections are usually acquired from the environment; however, dominant circulating clones (DCCs) have emerged recently in both M. abscessus subsp. massiliense and subsp. abscessus that appear to be transmitted among humans and are now globally distributed. These recently emerged clones are potentially informative about the ecological and evolutionary mechanisms of pathogen emergence and host adaptation. The geographical distribution of DCCs has been reported, but the genomic processes underlying their transition from environmental bacterium to human pathogen are not well characterized. To address this knowledge gap, we delineated the structure of M. abscessus subspecies abscessus and massiliense using genomic data from 200 clinical isolates of M. abscessus from seven geographical regions. We identified differences in overall patterns of lateral gene transfer (LGT) and barriers to LGT between subspecies and between environmental and host-adapted bacteria. We further characterized genome reorganization that accompanied bacterial host adaptation, inferring selection pressures acting at both genic and intergenic loci. We found that both subspecies encode an expansive pangenome with many genes at rare frequencies. Recombination appears more frequent in M. abscessus subsp. massiliense than in subsp. abscessus, consistent with prior reports. We found evidence suggesting that phage are exchanged between subspecies, despite genetic barriers evident elsewhere throughout the genome. Patterns of LGT differed according to niche, with less LGT observed among host-adapted DCCs versus environmental bacteria. We also found evidence suggesting that DCCs are under distinct selection pressures at both genic and intergenic sites. Our results indicate that host adaptation of M. abscessus was accompanied by major changes in genome evolution, including shifts in the apparent frequency of LGT and impacts of selection. Differences were evident among the DCCs as well, which varied in the degree of gene content remodelling, suggesting they were placed differently along the evolutionary trajectory toward host adaptation. These results provide insight into the evolutionary forces that reshape bacterial genomes as they emerge into the pathogenic niche.

The Gonococcal Genetic Island defines distinct sub-populations of Neisseria gonorrhoeae

“…This latter phenomenon is typical of bacteria undergoing host adaptation and consequent niche restriction [50][51][52][53][54]. We identified similar patterns of diversity in our comparative genomic study of host adaptation among Mycobacterium abscessus, where host adapted/niche-restricted strains appeared to have fewer opportunities to engage in HGT than environmental M. abscessus [55]. N. gonorrhoeae differs from M. abscessus in that it is a strict human pathogen, and we posit that observed differences between GGI+ and GGI− sub-populations reflect differential access to niches within the human body containing diverse pools of bacteria.…”

Comparative Genomics of Streptococcus oralis Identifies Large Scale Homologous Recombination and a Genetic Variant Associated with Infection

“…This indicates that S. oralis core genes are under strong purifying selection. We recently identified a similar phenomenon among environmental isolates of Mycobacterium abscessus that are also highly recombinogenic and manifest large amounts of synonymous diversity in their core genomes ( 50 ). This suggests that like M. abscessus , S. oralis inhabits environments alongside diverse microbial species where high rates of recombination enable the ready acquisition of novel genetic material and rapid removal of deleterious mutations.…”

Comparative genomics ofStreptococcus oralisidentifies large scale homologous recombination and a genetic variant associated with infection

“…This indicates that S. oralis core genes are under strong purifying selection. We recently identified a similar phenomenon among environmental isolates of Mycobacterium abscessus that are also highly recombinogenic and manifest high amounts of synonymous diversity in their core genomes ( 50 ). This suggests that like M. abscessus, S. oralis inhabits environments alongside diverse microbial species where high rates of recombination enable ready acquisition of novel genetic material and rapid removal of deleterious mutations.…”