Abstract

BackgroundLatin-American (LA) countries are among the largest mercury (Hg) polluters in the world. Fittingly, a significant high frequency (>50%) of Hg resistance genes (MRG) has been observed in LA MRSA genomes, including USA300-LV clone, which contains the genomic element COMER, encoding for copper and Hg resistance genes adjacent to SCCmecIVc/E. Co-selection of MRG and antibiotic resistance genes may be facilitated by shared transferable genetic elements, nevertheless, analyses of the genetic MRG context in strains other than USA300-LV are lacking. In this study, we aimed to characterize possible mechanisms of acquisition and transfer of MRG in LA S. aureus.MethodsWe sequenced 6 MRSA and 2 MSSA clinical isolates harboring MRG from Colombia, Ecuador, Peru and Chile using short-read (Illumina) and long-read (ONT) sequencing. Hybrid assemblies were constructed using Flye and iterative polishing with Medaka and Racon. Identification of insertion sequences, rearrangements and assessment of the genomic context was investigated using ISfinder, MAUVE, PlasmidFinder and SnapGene.ResultsHighly contiguous genome assemblies allowed us to identify the localization and genetic background of MRG. For MRSA belonging to USA300-LV (SCCmecIVc/E) and Brazilian (SCCmecIII) clones, we confirmed the presence of MRG within SCCmec. In contrast, for the 4 MRSA belonging to Chilean/Cordobes clone (SCCmecI), collected from Colombia, Chile and Peru, MRG were located on ~30kbp plasmids genetically related that also contained the blaZ beta-lactamase and cadmium/arsenic resistance genes. In MSSA strains, we observed both plasmidic and chromosomal localizations of MGR. Interestingly, in one of the MSSA, MRG were inserted downstream of orfX, along with repA, suggesting a plasmidic origin. In all these cases, MRG were flanked by IS6 family elements.ConclusionGenomic architecture of SCCmec types IVc/E and III might facilitate MRG transferability, whereas for the highly prevalent Chilean/Cordobes clone (SCCmecI) MRG acquisition occurs through plasmids. Our findings underscore the mechanisms of MRG transference in LA S. aureus likely related to antibiotic resistance co-selection.Disclosures Cesar A. Arias, MD, MSc, PhD, FIDSA, Entasis Therapeutics (Scientific Research Study Investigator)MeMed (Scientific Research Study Investigator)Merck (Grant/Research Support)

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