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.

Evaluation of analogs of mutacin 1140 in systemic and cutaneous methicillin-resistant Staphylococcus aureus infection models in mice

“…In a 2018 study, multilayered carbon nanotubes showed potential synergistic effect with methicillin when treating a multi-drug-resistant Pseudomonas aeruginosa infection ( Mousavi et al, 2018 ). In a recent study, a co-expression network of genes involved in cell wall synthesis following exposure to penicillin in an Escherichia coli resistance strain has provided new targets for drug development ( Shiri et al, 2020 ). Without the continued efforts made by academic research labs, the availability of useful approaches to mitigate human susceptibility to infections caused by drug-resistant bacteria will likely remain limited.…”

Beta-lactamase determinants and molecular typing of carbapenem-resistant classic and hypervirulent Klebsiella pneumoniae clinical isolates from southwest of Iran

“…A number of factors contribute to the difficulties in managing infections caused by CR-Kp, including simultaneous resistance to multiple antibiotic classes, poor patient clinical outcomes, and prolonged hospitalizations ( Vaez et al, 2019 ). Resistance to beta-lactam antibiotics, including carbapenems, is mediated by a network of different mechanisms and genes ( Dalmolin et al, 2017 ; Codjoe and Donkor, 2018 ; Shiri et al, 2020 ). The major mechanisms for carbapenem resistance in K. pneumoniae include the production of various beta-lactamases capable of hydrolyzing carbapenems as well as the reduced membrane permeability that occurs via loss or downregulation expression of outer membrane porins (OMPs) ( Dalmolin et al, 2017 ; Codjoe and Donkor, 2018 ).…”