Comparative genomics of methicillin-resistant and -susceptible Staphylococcus aureus from Mexico City hospitals

Methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) Staphylococcus aureus are major causes of hospital-acquired infections worldwide. However, their genomic features remain underexplored in many regions, particularly in low- and middle-income countries (LMICs). Here, we investigated the genomic diversity, antibiotic resistance, and virulence traits of methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) Staphylococcus aureus isolates from three tertiary care hospitals in Mexico City. A total of 101 isolates collected between 2006 and 2019 from newborns and adults with diverse infections were analyzed using whole-genome sequencing. MRSA isolates were restricted to clonal complexes CC5 and CC8, whereas MSSA strains displayed a broader diversity across multiple lineages. A distinct clade of CC8-MRSA isolates identified in 2013 among newborns was closely related to the USA300 lineage but carried SCC mec IVc without the Panton-Valentine leukocidin genes and the COMER island. Similarly, a localized cluster of CC5-MSSA isolates from neonates in 2012 showed genomic variations largely driven by prophage-associated elements. MRSA strains carried a higher burden of resistance genes, including fluoroquinolone-associated mutations, whereas MSSA isolates exhibited greater heterogeneity in virulence genes and spa types. Both groups shared a conserved virulence gene repertoire; however, variations in the virulence genes highlighted lineage-specific pathogenic features. IMPORTANCE MRSA and MSSA S. aureus genomes are still largely unstudied in Mexico although they are frequently found in hospitals. This study provides a long-term genomic analysis of MRSA and MSSA isolates from three hospitals in Mexico. Our findings revealed the presence of S. aureus international clones of clonal complexes CC5 and CC8 over a decade, broader diversity in MSSA, and localized clonal transmission within hospitals. The contrasting resistance and virulence profiles of MRSA and MSSA clones underscore the need for genomic surveillance frameworks to inform infection control and antibiotic stewardship in healthcare settings.