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.Communicated by Ramaswamy H. Sarma.

Genomic assortment and interactive insights of the chromosomal encoded control of cell death (ccd) toxin-antitoxin (TA) module in Xenorhabdus nematophila.

In the present circumstances, toxin-antitoxin (TA) modules have a great consideration due to their elusive role in bacterial physiology. TA modules consist of a toxic part and a counteracting antitoxin part and these are abundant genetic loci harbored on bacterial plasmids and chromosomes. The control of cell death (ccd) TA locus was the first identified TA module and its unitary function (such as plasmid maintenance) has been described, however, the function of its chromosomal counterparts is still ambiguous. Here, we are exploring the genomic assortment, structural and functional association of chromosomally encoded ccdAB TA homolog (ccdABXn1) in the genome of an entomopathogenic bacterium Xenorhabdus nematophila. This bacterium is a symbiotic model with the nematode Steinernema carpocapsae that infects and kills the host insect. By genomic assortment analysis, our observations suggested that CcdA antitoxin homologs are not more closely related than CcdB toxin homologs. Further results suggest that the ccdABXn1 TA homolog has sulphonamide (such as 4C6, for CcdA homolog) and peptide (such as gyrase, for CcdB homolog) ligand partners with a typical TA interaction network that may affect essential cellular metabolism of the X. nematophila. Collectively, our results improve the knowledge and conception of the metabolic interactive role of ccdAB TA homologs in X. nematophila physiology.Communicated by Ramaswamy H. Sarma.