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Communication Dans Un Congrès Année : 2018

In mycoplasma, horizontal chromosomal transfer could accelerate the emergence of antimicrobial resistance

Résumé

Background: In recent years, antimicrobial-resistance (AMR) has been reported for most bacterial pathogens, including mycoplasmas, and has become a major public health issue. One main driver of the AMR crisis is the rapid spreading of AMR genes or mutations via horizontal gene transfer (HGT). In mycoplasmas, this mechanism was long thought to play a minor role in AMR because of (i) the absence of plasmids in the majority of these minimal bacteria and (ii) resistance mechanisms relying mainly on mutations in target genes and not on acquisition of new plasmid-encoded genes. The discovery of massive, conjugative, chromosomal transfers in the ruminant pathogen Mycoplasma agalactiae (MA) prompted us to revisit the impact of this atypical HGT on mycoplasma AMR. For this purpose, we used MA as model and the enrofloxacin (Enro), a fluoroquinolone which targets type II topoisomerase. Methods: First, spontaneous MA EnroR mutants with diff erent MIC (Minimum Inhibitory Concentration) were obtained by serial in vitro passages of the EnroS-PG2 type strain using increasing Enro concentrations. These EnroR strains were then used as donors in mating experiments with the EnroS-5632 strain as recipient. A selection of 24 MA EnroR-mutants and -transconjugants were subjected to high-throughput sequencing to further (i) identify and map both AMR genetic determinants and transferred chromosomal regions, and (ii) reconstruct the dynamics of AMR acquisition. Results: Data showed that in spontaneous EnroR mutants, the serial increase in MIC values correlate with the sequential accumulation of mutations in 4 genes, resulting in amino acid substitutions. These are gyrA,gyrB and parC, parE, encoding the DNA gyrase and the topoisomerase IV, respectively, and known as fluoroquinolone targets. Mating experiments resulted in EnroR transconjugants displaying mosaic genomes (donor/recipient), with the simultaneous exchange of distant fragments carrying the mutated EnroRgenes (parE, parC and/or gyrA). Additionally, other multiple fragments were co-transferred all around the genome. The analysis of the impact of all exchanged fragments on AMR and fitness are being explored.Conclusions: Since most mycoplasmas are deprived of plasmids, this study demonstrates the importance of chromosomally mediated AMR in mycoplasmas, with cumulative and sequential mutations correlating with MIC values. More importantly, our data point towards HGT, and particularly chromosomal transfer, as a major contributor and an accelerator of AMR acquisition in mycoplasmas by allowing the concomitant transfer of multiple and dispersed mutations in one single event. These exchanges of chromosomal genes could contribute to the emergence and diffusion of AMR and could also be implicated in other adaptive process (virulence, host specificity).

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Bactériologie
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Dates et versions

hal-02933421 , version 1 (08-09-2020)

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  • HAL Id : hal-02933421 , version 1

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Marion Faucher, Laurent Xavier Nouvel, Emilie Dordet-Frisoni, Marc Serge Marenda, Florence Tardy, et al.. In mycoplasma, horizontal chromosomal transfer could accelerate the emergence of antimicrobial resistance. 22th Congress of the International Organization for Mycoplasmology (IOM), IOM, Jul 2018, Portsmouth, New Hampshire, United States. ⟨hal-02933421⟩
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