This review clarifies the crucial role of cell wall inhibitors in fighting bacterial infections and highlights that antibacterial agent act solely in peptidoglycan biosynthesis, necessitating ongoing innovation to address antibiotic resistance effectively. The bacterial cell wall, which mainly consists of peptidoglycan, is essential for maintaining bacterial shape and structural integrity, rendering it an effective target for antibiotics. Peptidoglycan biosynthesis includes three different stages: cytoplasmic precursor formation, membrane-associated lipid carrier transfer, and final assembly at the cell wall. Antibiotics that interfere with these processes, including fosfomycin, D-cycloserine, bacitracin, glycopeptides, and ẞ-lactam antibiotics, disrupt critical steps, causing bacterial cell lysis. While cell wall inhibitors show selective toxicity and are essential in treating Gram-positive, Gram-negative, and multidrug-resistant pathogens, the emergence of resistance mechanisms such as enzymatic inactivation, target modification, efflux pumps, reduced permeability, and biofilm formation poses significant clinical challenges. Strategies to counteract this resistance include novel ẞ-lactamase inhibitors, diagnostic advancements, and next-generation antibiotic development. By targeting specific stages of peptidoglycan biosynthesis, antibiotics effectively disrupt bacterial cell wall integrity. However, the rise of resistance mechanisms highlights the need for ongoing innovation in drug development and stewardship programs to preserve their utility. • This review underscores the critical role of cell wall inhibitors in combating bacterial infections by targeting peptidoglycan biosynthesis. • It details how antibiotics like fosfomycin, D-cycloserine, bacitracin, glycopeptides, and β-lactams disrupt key stages, leading to bacterial lysis. • The emergence of resistance mechanisms—including enzymatic inactivation, target modification, efflux pumps, and biofilm formation—poses major clinical challenges. • Innovative strategies, such as next-generation antibiotics and β-lactamase inhibitors, are essential to overcoming resistance and preserving antibiotic efficacy.
Gubran et al. (Sun,) studied this question.