Evolutionary thrift: mycobacteria repurpose plasmid diversity during adaptation of type VII secretion systems

Abstract

Mycobacteria have a distinct secretion system, termed type VII (T7SS), which is encoded by paralogous chromosomal loci (ESX) and associated with pathogenesis, conjugation, and metal homeostasis. Evolution of paralogous gene families is of interest because duplication is an important mechanism by which novel genes evolve, but there are potential conflicts between adaptive forces that stabilize duplications and those that enable evolution of new functions. Our objective was to delineate the adaptive forces underlying diversification of T7SS. Plasmid-borne ESX were described recently, and we found evidence that the initial duplication and divergence of ESX systems occurred on plasmids and was driven by selection for advantageous mutations. Plasmid conjugation has been linked to T7SS and type IV secretion systems (T4SS) in mycobacteria, and we discovered that T7SS and T4SS genes evolved in concert on the plasmids. We hypothesize that differentiation of plasmid ESX helps to prevent conjugation among cells harboring incompatible plasmids. Plasmid ESX appear to have been repurposed following migration to the chromosome, and there is evidence of positive selection driving further differentiation of chromosomal ESX. We hypothesize that ESX loci were initially stabilized on the chromosome by mediating their own transfer. These results emphasize the diverse adaptive paths underlying evolution of novelty, which in this case involved plasmid duplications, selection for advantageous mutations in the mobile and core genomes, migration of the loci between plasmids and chromosomes, and lateral transfer among chromosomes. We discuss further implications for the choice of model organism to study ESX functions in Mycobacterium tuberculosis.

Genomics of Atlantic Forest Mycobacteriaceae strains unravels a mobilome diversity with a novel integrative conjugative element and plasmids harbouring T7SS

“…In addition to the chromosomally encoded ESX-3 and ESX-4 systems, the host strain has an extra ESX-3 copy, which would impact the bacterial fitness in the environment. These results reinforce the hypothesis of the mobilization of the ESX-system through mobile genetic elements, which have driven its evolution and mobility [31–33].…”

“…However, to date, there is a lack of information regarding other mobile elements, such as plasmids and genomic islands. Even so, plasmids had a pivotal role in the evolution of this family, as they were involved in the diversification and mobility of T7SS [31–33]. Here, we explored the mobilome of Mycobacteriaceae strains from the soil of the Brazilian Atlantic Forest, which is one of the main biodiversity hotspots in the world and has a prevalence of Mycobacteriaceae [59, 60].…”

“…This set of genes has been shown to play a role in Mycobacterium plasmid conjugation [27]. T7SS is found at one copy in several Actinobacteria plasmids [27, 28, 30–33]. In fact, pCBMA213_1 and pCBMA213_2 encoded ESX-3-like and ESX-2-like, respectively.…”

“…These two ESX-systems carried by the CBMA plasmids have a close phylogenetic relationship with the ESX-systems of other distinct plasmids that are carried by several species from different niches (). The ESX-3 system is related to metal homeostasis, while the ESX-2 function is still unknown [33]. In addition to the chromosomally encoded ESX-3 and ESX-4 systems, the host strain has an extra ESX-3 copy, which would impact the bacterial fitness in the environment.…”

“…ESX-3 is considered essential for the survival of mycobacteria, as it is involved with the uptake of iron and zinc. The function of the ESX-2 is still unknown [31–33]. Other mobilome elements, as the integrative conjugative elements, are also rare in this bacterial family.…”