Computational exploration of the genomic assignments, molecular structure, and dynamics of the ccdABXn2 toxin-antitoxin homolog with its bacterial target, the DNA gyrase, in the entomopathogen Xenorhabdus nematophila

Toxin-antitoxin (TA) modules, initially discovered on bacterial plasmids and subsequently identified within chromosomal contexts, hold a pivotal role in the realm of bacterial physiology. Among these, the pioneering TA system, ccd (Control of Cell Death), primarily localized on the F-plasmid, is known for its orchestration of plasmid replication with cellular division. Nonetheless, the precise functions of such systems within bacterial chromosomal settings remain a compelling subject that demands deeper investigation. To bridge this knowledge gap, our study focuses on exploring ccdABXn2, a chromosomally encoded TA module originating from the entomopathogenic bacterium Xenorhabdus nematophila. We meticulously delved into the system's genomic assignments, structural attributes, and functional interplay. Our findings uncovered intriguing patterns-CcdB toxin homologs exhibited higher conservation levels compared to their CcdA antitoxin counterparts. Moreover, we constructed secondary as well as tertiary models for both the CcdB toxin and CcdA antitoxin using threading techniques and subsequently validated their structural integrity. Our exploration extended to the identification of key interactions, including the peptide interaction with gyrase for the CcdB homolog and CcdB toxin interactions for the CcdA homolog, highlighting the intricate TA interaction network. Through docking and simulation analyses, we unequivocally demonstrated the inhibition of replication via binding the CcdB toxin to its target, DNA gyrase. These insights provide valuable knowledge about the metabolic and physiological roles of the chromosomally encoded ccdABXn2 TA module within the context of X. nematophila, significantly enhancing our comprehension of its functional significance within the intricate ecosystem of the bacterial host.