Peptidoglycan recycling is critical for cell division, cell wall integrity and β-lactam resistance in Caulobacter crescentus

Most bacteria possess a peptidoglycan cell wall, which is continuously remodeled during cell growth and divi¬sion. The peptidoglycan (PG) fragments generated in this process are typically imported into the cell and recycles through the PG biosynthesis pathway. While the underlying pathways have been studied intens¬ively in gamma¬proteobacteria, knowledge of their presence and physiological roles in other bacterial line¬ages remains limited. Here, we comprehensively investigate PG recycling in the alphaproteo¬bacterial model organism Caulo¬bacter crescentus. We show that this species contains a func¬tional PG recycling pathway by char¬acterizing the activities of key enzymes both in vitro and in vivo. Our results reveal that PG recycling is critical for maintaining C. crescentus cell morphology and division and is dynamically regu¬lated to balance the flux of metabolic intermediates toward PG biosynthesis and central carbon metabol¬ism. Im¬portantly, defects in PG recyc¬ling strongly impair the intrinsic ampicillin resistance of C. crescentus without changing the activity of its β-lactamase BlaA, likely by limiting PG precursor biosynthesis and thereby increasing the sensitivity of the septal FtsW-FtsI com-plex to residual antibiotic molecules. These findings underscore the central role of PG recyc¬¬ling in bacterial fitness and suggest that inhibiting this process could provide a promising strategy to combat β-lactam-resistant pathogens.