Re-construction of Co-expression Network of Genes Involved in Bacterial Cell Wall Synthesis and Their Role in Penicillin Resistance

Abstract

Background: Peptidoglycan (Murein), which consists of disaccharide and amino acid chain subunits, has a key role in bacterial survival and ranks first in the line defense system against drug therapy. In addition, the transpeptidase enzyme plays an important role in cross-linking in bacterial cell walls. In Escherichia coli bacteria, cross-linking happens by proteins that have a D-D transpeptidase role and bond two amino acids of D-alanine together. These proteins are characterized by their affinity for and binding of penicillin thus they are called penicillin-binding proteins (PBPs). It should be noted that this bonding formation is prevented by the beta-lactam family as they have a similar structure to the above-mentioned proteins. The product of the idtD gene by characteristics such as L-D transpeptidase can catalyze the peptidoglycan structure in the bacterial cell wall in the presence of beta-lactam antibiotics. Methods: In this study, around 426 interactions were identified between genes and approximately 20 genes with a key role in the process of bacterial cell wall synthesis by the reconstruction of 44 genes involved in bacterial cell wall synthesis. Results: The idtD gene locus at the reconstructed network clearly shows that its catalytic activity is the side activity, and there won’t be a lag or disturbance in the procedure cell wall synthesis by removing it from the cycle. However, this side process causes the strengthening of the bacterial cell wall synthesis process against disorders arising by the presence of beta-lactam antibiotics. Conclusions: These five genes in E. coli that furnish L-D transpeptidase properties include IdtA, IdtC, IdtD, IdtE, and mrdA out of which, IdtD is the most important gene in this process.