β-Lactam Resistance in ESKAPE Pathogens Mediated Through Modifications in Penicillin-Binding Proteins: An Overview

Bacteria acquire β-lactam resistance through a multitude of mechanisms among which production of β-lactamases (enzymes that hydrolyze β-lactams) is the most common, especially in Gram-negatives. Structural changes in the high-molecular-weight, essential penicillin-binding proteins (PBPs) are widespread in Gram-positives and increasingly reported in Gram-negatives. PBP-mediated resistance is largely achieved by accumulation of mutation(s) resulting in reduced binding affinities of β-lactams. Herein, we discuss PBP-mediated resistance among ESKAPE pathogens that cause diverse hospital- and community-acquired infections globally. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40121-023-00771-8.