Genetic architecture and functional dynamics of integrons in Staphylococcus aureus resistance

Staphylococcus aureus is a major opportunistic pathogen and a leading cause of community and hospital-acquired infections worldwide, with a growing capacity to develop multidrug resistance (MDR). Among the genetic mechanisms driving this resistance, integrons play a critical role by capturing, rearranging, and expressing antimicrobial resistance gene cassettes through site-specific recombination. Although integrons are traditionally associated with Gram-negative bacteria, increasing evidence highlights their significant contribution to resistance dissemination in S. aureus, particularly in methicillin-resistant S. aureus (MRSA) strains. This review focuses on current knowledge on the structure, function, and types of integrons, and their role in prevalence and mechanistic role in S. aureus. Integrons interact with other mobile genetic elements like transposons and plasmids to enable horizontal gene transfer across strains and species. Among the four recognized classes of integrons, class 1 is the most prevalent in S. aureus frequently associated with plasmids and transposons and show resistance to β-lactams, aminoglycosides, fluoroquinolones, and tetracyclines. Class 2 integrons occur less commonly and exhibit limited cassette diversity, while class 3 integrons remain rare. Epidemiological studies report class 1 integron prevalence ranging from 40 to 70% in clinical isolates across different regions, often correlating with resistance to β-lactams, aminoglycosides, fluoroquinolones, tetracyclines, and rifampicin, and co-occurring with SCCmec elements in MRSA. Integron-mediated resistance is further enhanced by stress-induced integrase activity and biofilm formation, promoting persistence in healthcare settings. Molecular detection methods, particularly multiplex PCR targeting integrase genes, are essential for surveillance. Understanding integron dynamics in S. aureus is crucial for informing antimicrobial stewardship, infection control strategies, and future interventions aimed at limiting the spread of MDR pathogens.