Beyond the Wild MRSA: Genetic Features and Phylogenomic Review of -Mediated Methicillin Resistance in Non- Staphylococci and Mammaliicocci

Methicillin resistance, mediated by the gene in staphylococci and mammaliicocci, has caused tremendous setbacks in the use of antibiotics in human and veterinary medicine due to its high potential of presenting the multidrug resistance (MDR) phenotype. Three other analogs exist, of which the has evolutionary been associated with methicillin-resistant (MRSA) in wild animals, thus loosely referred to as the wild MRSA. In this study, we present an epidemiological review and genomic analysis of non- staphylococci and mammaliicocci that carry the -mediated methicillin resistance trait and determine whether this trait has any relevant link with the One Health niches. All previous studies (2007 till 2023) that described the gene in non- staphylococci and mammaliicocci were obtained from bibliometric databases, reviewed, and systematically analyzed to obtain the antimicrobial resistance (AMR) and virulence determinants, mobilome, and other genetic contents. Moreover, core genome single-nucleotide polymorphism analysis was used to assess the relatedness of these strains. Of the 533 articles analyzed, only 16 studies (on livestock, environmental samples, milk bulk tanks, and wild animals) were eligible for inclusion, of which 17 genomes from 6 studies were used for various in silico genetic analyses. Findings from this systematic review show that all -carrying non- staphylococci were resistant to only beta-lactam antibiotics and associated with the classical SCC XI of . Similarly, two studies on wild animals reported -carrying associated with SCC XI. Nevertheless, most of the -carrying species presented an MDR phenotype (including linezolid) and carried the SCC- hybrid associated with The phylogenetic analysis of the 17 genomes revealed close relatedness (<20 SNPs) and potential transmission of and strains in livestock farms in Algeria, Tunisia, and Brazil. Furthermore, closely related strains from Austria, Brazil, and Tunisia (<40 SNPs) were identified. This systematic review enhances our comprehension of the epidemiology and genetic organization of within the non- staphylococci and mammaliicocci. It could be hypothesized that the -carrying non- staphylococci are evolutionarily related to the wild MRSA-. The potential implications of clonal development of a lineage of carrying strains across multiple dairy farms in a vast geographical region with the dissemination of MDR phenotype is envisaged. It was observed that most -carrying non- staphylococci and mammaliicocci were reported in mastitis cases. Therefore, veterinarians and veterinary microbiology laboratories must remain vigilant regarding the potential existence of strains originating from mastitis as a potential niche for this resistance trait.