Analysis of the genome sequence of the hedgehog-associated mecC- MRSA CC599

After the discovery of mecC, an alternative gene conferring beta-lactam resistance to Staphylococcus (S.) aureus, epidemiological studies suggested a zoonotic background of mecC-MRSA. These strains are associated with hedgehogs (Erinaceus europaeus) where they appear to have evolved under selective pressure exerted by penicillin-producing dermatophytes (Trichophyton erinacei). CC599 is one mecC-MRSA lineage and the aim of this study was to characterise it further. Four genome sequences of CC599-MRSA-XI isolates from three hedgehogs from Jena, Thuringia, were obtained by nanopore sequencing. One isolate originated from a nasopharyngeal swab of a road-killed hedgehog. The second isolate was cultured from homogenised ticks collected from a gravely ill hedgehog. Because of morphological differences, two subclones were sequenced. A third isolate came from a hedgehog that was infected with T. erinacei as well as with CC130- and CC599-MRSA. The studied isolates carried SCCmec XI elements identical to those from other mecC-MRSA lineages. This also included a specific penicillinase gene and an arsenic resistance operon. Isolates carried two pathogenicity islands, one of them harbouring genes for enterotoxins C and L (sec, sel), and for the toxic shock syndrome toxin (tst1). Other virulence factors included enterotoxin genes seli2=sel26 and selu2=sel27 as well as leukocidin genes lukD/E. The prophage carriage was variable. Mitomycin C induction followed by nanopore sequencing and transmission electron microscopy yielded Dubowvirus-like particles as well as particles with the tst1/sec/sel pathogenicity island. Among 65 hedgehogs sampled in 2024-2026 in and around Jena, seven had mecC-MRSA. In addition, three cases of mecC-MRSA were identified by random sampling in the years before. Five hedgehogs carried CC599-MRSA-XI; four, CC130-MRSA-XI and one had both MRSA strains. CC599-MRSA-XI has also been found in humans, but this is rare. No CC599 isolate was found among 1,800 clinical MRSA isolates collected over 20 years at Dresden University Hospital. Among 3,000 MRSA collected 2010 to 2019 at Regensburg University Hospital, five belonged to this strain while a second sampling period, 2020 to 2024 yielded as many as six CC599-MRSA-XI among a total of 518 MRSA isolates. Some human isolates differed from hedgehog isolates, either in an absence of the tst1/sec/sel pathogenicity island, or in a presence of a CRISPR/cas operon localised downstream of SCCmec. In conclusion, CC599-MRSA-XI is a hedgehog-associated mecC-MRSA strain. It carries virulence factors that are also relevant to humans, and it may have zoonotic potential.