Geographic divergence of methicillin-resistant <i>Staphylococcus aureus</i> ST5-SCC <i>mec</i> I in the aftermath of a major earthquake and tsunami: impact of a plasmid harboring heavy metal resistance genes

Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) is a major public health menace. The global spread of MRSA is characterized by successive waves of epidemic clones dominating specific geographical regions. The acquisition of genes encoding resistance to heavy metals (HMRGs) is thought to be a key feature in the geographic divergence of MRSA. However, the cause-effect relationship between the presence of HMRGs and the divergence of MRSA clones remains to be clarified. In this study, we assessed the role that HMRGs may have played in the evolutionary divergence of the MRSA ST5-SCC<i>mec</i>I lineage in Latin America. We conducted a genomic characterization of 113 MRSA clinical isolates from six Latin American healthcare centers, including 53 isolates collected from two cities in Chile (Santiago and Concepción). We found a plasmid (pSCL4752) harboring arsenic, cadmium, and mercury resistance genes in 65% (<i>n</i> = 71) of the ST5-SCC<i>mec</i>I isolates. We also observed a geographic divergence associated with the presence of pSCL4752 in Chilean isolates, with a higher frequency in isolates from Concepción (88%) compared to Santiago (29%). Interestingly, a molecular clock analysis revealed that this divergence occurred in the aftermath of an 8.8 Mw earthquake and tsunami that struck the Concepción area in 2010. Moreover, our results demonstrate that the carriage of pSCL4752 can be beneficial or detrimental for ST5-SCC<i>mec</i>I isolates, depending on the environmental availability of these heavy metals. Our results suggest that the divergence of the ST5-SCC<i>mec</i>I MRSA lineage in Latin America could have been fostered by environmental disasters and influenced by the presence/absence of HMRGs harbored in a plasmid.IMPORTANCEMethicillin-resistant <i>Staphylococcus aureus</i> (MRSA) is a major cause of life-threatening infections worldwide and a growing public health concern. The rise of antibiotic-resistant bacteria, such as MRSA, is often linked to genetic adaptations that enhance their survival. Our research sheds light on how environmental changes, such as those triggered by a natural disaster, can influence the evolution and geographic spread of a highly resistant MRSA lineage in Latin America. We identified a plasmid carrying genes for resistance to arsenic, cadmium, and mercury, which was associated with the geographic divergence of the ST5-SCC<i>mec</i>I MRSA lineage, with striking differences in its prevalence between regions affected by a major earthquake and tsunami. By linking environmental events to pathogen evolution, our study highlights the role of ecological pressures in the spread of MRSA. These findings emphasize the need to integrate environmental monitoring into public health strategies to better understand the global challenge of antimicrobial resistance.