Genomic profiling and molecular dynamics analysis of toxin-antitoxin homologs targeting DNA gyrase in : insights from computational investigations.

In the realm of hospital-acquired and chronic infections, stands out, demonstrating significant associations with increased morbidity, mortality, and antibiotic resistance. Antibiotic-resistant strains are believed to contribute to thousands of deaths each year. Chronic and latent infections are associated with the bacterial toxin-antitoxin (TA) system, although the mechanisms involved are poorly understood. This study focuses on a novel type II TA system, , identified in the genome of ATCC 27853. We explored its structural features, functional relationships, and genetic configurations. Our research identified homologs in , clarified their interactions, and highlighted connections to essential cellular metabolic processes. Notably, homologs of the ParD antitoxin were found to be more conserved than the ParE toxin. Structural models of the ParE toxin and ParD antitoxin confirmed their integrity. Through docking and molecular dynamics simulations, we showed that the ParE toxin binds to DNA gyrase, inhibiting replication. The stability of the ParD-ParE complex is primarily driven by hydrophobic interactions (-1763.2 kcal/mol), while the ParE-GyrA interaction is sustained by strong electrostatic forces (-1294.9 kcal/mol). The RMSD scores indicated greater stability for the ParD-ParE complex (1.11 Å) than the ParE-GyrA complex (1.16 Å). RMSF analysis identified key residues involved in the ParD-ParE complex (Leu, Gly, Arg, Asn, Arg) and the ParE-GyrA complex (Pro, Gln, Ser, Asp, Gln). These findings significantly enhance our understanding of the structural and metabolic roles of the chromosomally encoded TA module in