Plasmids in Staphylococcus aureus: key vectors of antibiotic resistance genes dissemination

International audience

English. Background and objectives: Staphylococcus aureus (SA) possesses a wide variety of antibiotic resistance genes (ARGs), and their dissemination is closely associated with the high proportion of mobile genetic elements (MGEs) present in SA genomes (between 15 and 20%). To date, few data are available on the diversity of ARG-carrying MGEs in SA, and their impact on the spread of antibiotic resistance is poorly documented.Methods: An in silico analysis of 9054 human- and animal-associated SA genomes available in NCBI databases was carried out. An exhaustive mapping of associations between MGE, ARG and hosts was established using the ResFinder, RGI-CARD and MEFinder tools. In parallel, an in vitro analysis of 329 SA isolates collected from animals through the Resapath network between 2010 and 2021 and carrying ARGs was carried out. Plasmids were characterized by PFGE and the ARGs they carried determined by PCR. All identified plasmids were long-read sequenced (MinION) and a subset of 81 isolates were short-read sequenced (Illumina).Results: In silico analyses of SA genomes identified 88 different ARGs and 305 different MGEs, including 167 plasmids (identified using the rep gene), 25 transposons and 14 integrative and conjugative elements. Exploration of the MGE/ARG associations revealed that ARGs were predominantly present on plasmids (62%) and transposons (37%, with 2% associated with plasmids). Given their importance as ARG carriers, 211 plasmids collected from 329 SA isolates of animal origin in France over a ten-year period were characterized. The major families identified —rep7a, rep20, and rep10— were associated with specific resistance genes (str, cat, blaZ, erm(C)) and exhibited widespread horizontal transfer across different SA sequence types and animal hosts. Evolution of plasmids was observed, since the rep7a/str and rep7a/cat plasmids, circulating in horses, were progressively replaced by a rep7a plasmid carrying both str and cat genes. The study also highlighted the presence of mosaic (combining elements from different bacterial species/genera) and hybrid (displaying more than one rep gene) plasmids. Conclusions: The diversity of MGEs and the predominance of ARG/plasmid associations confirmed that MGEs, and plasmids in particular, play a key role in the transmission of resistance in SA, whatever the host. It is therefore essential to characterize the transmission mechanisms of these elements in order to understand and better control the spread of antibiotic resistance in this major pathogen.