Antibiotics and Antibiotic Resistance—Mur Ligases as an Antibacterial Target

Abstract

The emergence of Multidrug Resistance (MDR) strains of bacteria has accelerated the search for new antibacterials. The specific bacterial peptidoglycan biosynthetic pathway represents opportunities for the development of novel antibacterial agents. Among the enzymes involved, Mur ligases, described herein, and especially the amide ligases MurC-F are key targets for the discovery of multi-inhibitors, as they share common active sites and structural features.

What is the role of microbial biotechnology and genetic engineering in medicine?

“…However, the onset of resistance to glycopeptides in major pathogens has been delayed compared to β‐lactam antibiotics (Santos‐Beneit, Ordóñez‐Robles, et al, 2017 ). Lipopeptides are amphiphilic molecules containing a short linear or cyclic oligopeptide (polar moiety) and a linear or branched fatty acid of varying lengths (apolar moiety) (Hervin et al, 2023 ). Daptomycin, approved for clinical use at the beginning of the 21st century, has a distinct mechanism of action compared to β‐lactam antibiotics or glycopeptide antibiotics, disrupting multiple aspects of bacterial cell membrane function (Butler et al, 2023 ).…”

Unveiling the Multifaceted Capabilities of Endophytic Aspergillus flavus Isolated from Annona squamosa Fruit Peels against Staphylococcus Isolates and HCoV 229E—In Vitro and In Silico Investigations

“…Typically, the product binds predominantly across the central domain of the ligase protein near the ATP-binding site (Figure 8A). Several MRSA MurE key residues have been reported as important, including Asp406, Ser456, and Glu460, for product/substrate binding and recognition [60], as well as an affinity for promising inhibitors [88][89][90][91]. Both the negatively charged sidechains of Asp406 and Glu460 as well as the polar mainchain of Ser456 served as the electrostatic trap mediating the stability of UNAM-tripeptide at the binding site.…”