Understanding bacterial strategies for coping with heavy metal stress is essential for elucidating their resilience in contaminated environments. However, whether cell wall exfoliation contributes to bacterial tolerance under heavy metal stress, such as cadmium (Cd) exposure, remains unclear and requires further investigation. In this study, we reveal a novel self-protective mechanism in Stenotrophomonas sp. H225 isolated from a Cd-contaminated farmland soil, which underwent controlled cell wall exfoliation and regeneration in response to Cd stress up to 200 mg L-1. Transmission electron microscopy and energy-dispersive X-ray spectroscopy analyses revealed that the exfoliated cell wall fragments served as extracellular Cd sinks, thereby reducing intracellular Cd accumulation. Fourier-transform infrared spectroscopy and enzyme-linked immunosorbent assay indicated progressive peptidoglycan (PG) degradation, with exfoliated PG concentration in solution increasing from 148 ng mL-1 at 0 mg L-1 Cd to 240 ng mL-1 at 200 mg L-1 Cd. This degradation was counteracted by the compensatory upregulation of PG biosynthesis genes, with the enrichment ratio reaching up to 0.83, facilitating cell wall reconstruction. Transcriptomic analysis and gene knockout experiments identified mtgA (encoding a monofunctional transglycosylase) as a key determinant in cell wall repair and Cd resistance. To our knowledge, this is the first mechanistic evidence that bacteria can mitigate heavy metal toxicity through dynamic cell wall remodeling involving exfoliation and regeneration. This finding enhances our understanding of microbial survival strategies under environmental stress and highlights potential targets for engineering metal-tolerant strains for bioremediation applications.
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