RESUMEN
Antibiotic resistance genes (ARGs) in Staphylococcus aureus can disseminate vertically through successful clones, but also horizontally through the transfer of genes conveyed by mobile genetic elements (MGEs). Even though underexplored, MGE/ARG associations in S. aureus favor the emergence of multidrug-resistant clones, which are challenging therapeutic success in both human and animal health. This study investigated the interplay between the mobilome and the resistome of more than 10,000 S. aureus genomes from human and animal origin. The analysis revealed a remarkable diversity of MGEs and ARGs, with plasmids and transposons being the main carriers of ARGs. Numerous MGE/ARG associations were identified, suggesting that MGEs play a critical role in the dissemination of resistance. A high degree of similarity was observed in MGE/ARG associations between human and animal isolates, highlighting the potential for unrestricted spread of ARGs between hosts. Our results showed that in parallel to clonal expansion, MGEs and their associated ARGs can spread across different strain types sequence types (STs), favoring the evolution of these clones and their adaptation in selective environments. The high variability of MGE/ARG associations within individual STs and their spread across several STs highlight the crucial role of MGEs in shaping the S. aureus resistome. Overall, this study provides valuable insights into the complex interplay between MGEs and ARGs in S. aureus, emphasizing the need to elucidate the mechanisms governing the epidemic success of MGEs, particularly those implicated in ARG transfer.IMPORTANCEThe research presented in this article highlights the importance of understanding the interactions between mobile genetic elements (MGEs) and antibiotic resistance genes (ARGs) carried by Staphylococcus aureus, a versatile bacterium that can be both a harmless commensal and a dangerous pathogen for humans and animals. S. aureus has a great capacity to acquire and disseminate ARGs, enabling efficient adaption to various environmental or clinical conditions. By analyzing a large data set of S. aureus genomes, we highlighted the substantial role of MGEs, particularly plasmids and transposons, in disseminating ARGs within and between S. aureus populations, bypassing host barriers. Given that multidrug-resistant S. aureus strains are classified as a high-priority pathogen by global health organizations, this knowledge is crucial for understanding the complex dynamics of transmission of antibiotic resistance in this species.
RESUMEN
DNA methylations play an important role in the biology of bacteria. Often associated with restriction modification (RM) systems, they are important drivers of bacterial evolution interfering in horizontal gene transfer events by providing a defence against foreign DNA invasion or by favouring genetic transfer through production of recombinogenic DNA ends. Little is known regarding the methylome of the Mycoplasma genus, which encompasses several pathogenic species with small genomes. Here, genome-wide detection of DNA methylations was conducted using single molecule real-time (SMRT) and bisulphite sequencing in several strains of Mycoplasma agalactiae, an important ruminant pathogen and a model organism. Combined with whole-genome analysis, this allowed the identification of 19 methylated motifs associated with three orphan methyltransferases (MTases) and eight RM systems. All systems had a homolog in at least one phylogenetically distinct Mycoplasma spp. Our study also revealed that several superimposed genetic events may participate in the M. agalactiae dynamic epigenomic landscape. These included (i) DNA shuffling and frameshift mutations that affect the MTase and restriction endonuclease content of a clonal population and (ii) gene duplication, erosion, and horizontal transfer that modulate MTase and RM repertoires of the species. Some of these systems were experimentally shown to play a major role in mycoplasma conjugative, horizontal DNA transfer. While the versatility of DNA methylation may contribute to regulating essential biological functions at cell and population levels, RM systems may be key in mycoplasma genome evolution and adaptation by controlling horizontal gene transfers.