Since their discovery, antibiotics have found extensive use not only in clinical settings but also in several industrial fields from agriculture and livestock, to biotechnology and research purposes.

As large amounts of antibiotics are used for human and animal therapy, new resistant pathogenic strains are continuously emerging, rendering the currently known antibiotics inefficient. Therefore, multidrug resistance in bacteria poses a serious clinical and economical issue, in particular within the health systems. In fact, deaths associated to multidrug resistant microorganisms, in Europe alone, have reached worrying numbers, with more than thirty thousand people dying as a direct consequence of such infections in 2020.

Penicillin-resistant strains are nowadays present in every country as a direct result of acquired resistance mechanisms arising from gene transfer and recombination. One significant mechanism involves the transfer of pbp genes, encoding for low-affinity penicillin-binding proteins (PBPs) that retain cell wall synthesis activity even in the presence of most antibiotics.

Current research on antibiotics focuses on the design and discovery of new molecules able to block the activity of PBPs, either by targeting their catalytic or allosteric sites. While targeting the active site may require the putative new drugs to contain lactam moieties, allosteric modulation may be achieved with completely different new structures for which bacteria have not yet developed resistance mechanisms.

This topic approaches all aspects regarding the modulation of PBPs and β-lactamases activities, focusing on the discovery of new molecules targeting their active or allosteric sites, insights on the structure of these proteins and mechanisms of acquired resistance to known and new compounds. Research papers on the structure-activity relationships and virtual screening-resulting information, focused on the interactions of small molecules with the relevant biological targets, and review articles on the subject will be considered.

The topic intends to collect key contributions to overcome multi-drug resistance prompted by PBPs and β-lactamases .

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Frontiers in Cellular and Infection Microbiology

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