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The integrity of this protective barrier must be maintained across the diversity of environmental conditions wherein bacteria replicate. However, at the cell surface, the cell wall and its synthesis machinery face unique challenges that threaten their integrity. Directly exposed to the extracellular environment, the peptidoglycan synthesis machinery encounters dynamic and extreme physicochemical conditions, which may impair enzymatic activity and critical protein-protein interactions. Biotic and abiotic stressors\u2014including host defenses, cell wall active antibiotics, and predatory bacteria and phage\u2014also jeopardize peptidoglycan integrity by introducing lesions, which must be rapidly repaired to prevent cell lysis. 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