Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) represents a significant public health challenge. In New Zealand, the community-associated MRSA sequence type (ST)5, carrying the staphylococcal cassette chromosome mec (SCCmec) type IV genetic element (which confers methicillin resistance), has been predominant since its detection in 2005. Known informally as the AK3 strain, it also exhibits resistance to fusidic acid. Here, we investigated the genomic evolution of the AK3 strain by analysing 397 genomes, comprising 361 MRSA and 36 closely related methicillin-susceptible S. aureus (MSSA) genomes, including 285 recently sequenced isolates from New Zealand spanning 2020 (n=30), 2021 (n=77), 2022 (n=88), 2023 (n=73) and 2024 (n=17). Phylogenetic analysis revealed that the AK3 strain evolved through stepwise acquisition of mobile genetic elements, with an MSSA ancestor likely introduced to New Zealand in the late 1970s. The lineage first acquired a SaPITokyo12571-like pathogenicity island, which contains the staphylococcal enterotoxin C bovine variant (sec-bov) and an enterotoxin-like protein (sel), between 1984 and 1991. This was followed by the integration of SCCmec type IV and adjacent fusidic acid resistance operon between 1997 and 2000. This timing coincides with increased community fusidic acid use in New Zealand. The AK3 strain then diversified into three major clades, spreading throughout New Zealand and Australia, with sporadic detection in European countries and Samoa. Our findings demonstrate how the sequential acquisition of mobile genetic elements, combined with antibiotic selection pressure, likely contributed to the successful emergence of AK3 and its spread in the South Pacific region.