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Dordet-Frisoni, E.

Publications and source records attributed to Dordet-Frisoni, E..

3 recordsLinked to original sources

The interplay between Mobilome and Resistome in Staphylococcus aureus

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). The underexplored MGE/ARG associations in S. aureus favor the emergence of multidrug-resistant clones, posing a significant threat to human and animal health. This study investigated the interplay between the mobilome, encompassing MGEs, and the resistome, the collection of ARGs, in more than 10,000 S. aureus genomes from human and animal sources. The analysis revealed a remarkable diversity of MGEs and ARGs, with plasmids and transposons being the main carriers of resistance genes. Numerous MGE/ARG associations were identified, suggesting that MGEs play a critical role in the dissemination of resistance. A high degree of similaritywas observed in MGE/ARG associations between human and animal isolates, highlighting the potential for unrestricted spread of ARGs between hosts. While clonal expansion is a major driver of resistance dissemination in S. aureus, our results showed that MGEs and their associated ARGs can spread across different strain 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 the ir 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 crucial 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 strains represent a major threat due to their ability to rapidly acquire and disseminate ARGs. By analyzing a large dataset of S. aureus genomes, we highlighted the substantial role of MGEs, in particular plasmids and transposons, in the dissemination of ARGs within and between S. aureus populations, bypassing the host barrier. Given that multidrug-resistant S. aureus strains are classified as a high-prioritypathogenby global health organizations, this knowledge is crucial for understanding the complex dynamics of transmission of antibiotic resistance in this species.

microbiology↗

Impacts of Mycoplasma agalactiae restriction-modification systems on pan-epigenome dynamics and genome plasticity

DNA methylation plays an important role in the biology of bacteria. Often associated with restriction modification (RM) systems, they also provide a defence against foreign DNA. Little is known regarding the methylome of the mycoplasma genus, which encompasses several pathogenic species with small genomes. Here, single molecule real-time (SMRT) and bisulphite sequencing combined with whole-genome analysis identified 19 methylated motifs associated with three orphan methyltransferases (MTases) and eight RM systems in Mycoplasma agalactiae, a ruminant pathogen and a model organism. 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 epigenome 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.

microbiology↗

The Integrative Conjugative Element (ICE) of Mycoplasma agalactiae: key elements involved in horizontal dissemination and influence of co-resident ICEs

The discovery of integrative conjugative elements (ICEs) in wall-less mycoplasmas and the demonstration of their role in massive gene flows within and across species has shed new light on the evolution of these minimal bacteria. Of these, ICEA of the ruminant pathogen Mycoplasma agalactiae represents a prototype and belongs to a new clade of the Mutatorlike superfamily that has no preferential insertion site and often occurs as multiple chromosomal copies. Here, functional genomics and mating experiments were combined to address ICEA functions and define the minimal ICEA chassis conferring conjugative properties to M. agalactiae. Data further indicated a complex interaction among co-resident ICEAs, since the minimal ICEA structure was influenced by the occurrence of additional ICEA copies that can trans-complement conjugative-deficient ICEAs. However, this cooperative behavior was limited to the CDS14 surface lipoprotein, which is constitutively expressed by co-resident ICEAs, and did not extend to other ICEA proteins including the cis-acting DDE recombinase and components of the mating channel whose expression was only sporadically detected. Remarkably, conjugative-deficient mutants containing a single ICEA copy knocked-out in cdsl4 can be complemented by neighboring cells expressing CDS14. This result, together with the conservation of CDS14 functions in closely related species, may suggest a way for mycoplasma ICEs to extend their interaction outside of their chromosomal environment. Overall, this study provides a first model of conjugative transfer in mycoplasmas and offers valuable insights towards the understanding of horizontal gene transfer in this highly adaptive and diverse group of minimal bacteria.\n\nIMPRTANCEIntegrative conjugative elements (ICEs) are self-transmissible mobile genetic elements that are key mediators of horizontal gene flow in bacteria. Recently, a new category of ICEs has been identified that confer conjugative properties to mycoplasmas, a highly adaptive and diverse group of wall-less bacteria with reduced genomes. Unlike classical ICEs, these mobile elements have no preferential insertion specificity and multiple mycoplasma ICE copies can be found randomly integrated into the host chromosome. Here, the prototype ICE of Mycoplasma agalactiae was used to define the minimal conjugative machinery and propose the first model of ICE transfer in mycoplasmas. This model unveils the complex interactions taking place among co-resident ICEs and suggests a way for these elements to extend their influence outside of their chromosomal environment. These data pave the way for future studies aiming at deciphering chromosomal transfer, an unconventional mechanism of DNA swapping that has been recently associated with mycoplasma ICEs.

microbiology↗