Bibliogr.

Toxin–antitoxin (TA) systems consist of toxic proteins and their inhibitors, and were originally shown to ensure plasmid maintenance in bacterial populations. Over time, however, TA systems have also been identified on bacterial chromosomes, raising questions about their roles unrelated to plasmid stability. Among the eight currently recognized types of TA systems, type II has been the most extensively investigated. Type II systems are often found in pathogenic bacterial species, including staphylococci. Staphylococcus aureus, a notorious human pathogen, harbors multiple type II TA systems, both plasmid- and chromosome-encoded, while their potential relation to virulence remains to be addressed. Here, we investigate the co-occurrence of TA systems and antibiotic resistance (AR) determinants in S. aureus, focusing on the potential negative impact of type II toxin RNases on antibiotic resistance. We considered both well-characterized and newly characterized TA loci of S. aureus. Our findings demonstrate a relationship between TA systems and AR determinants, wherein TA systems negatively affect antibiotic resistance. Due to substantial selective pressure, the migration of TA systems from plasmids to chromosomes results in their inactivation. This observation may be an important factor shaping the spread and evolution of both TA systems and AR determinants in bacteria. We exemplify this phenomenon in detail using the well-known PemIK-Sa1 system and a newly identified SCCmec-related PemIK-Sa6 system characterized in this study.