2026-10-14T15:42:56Z https://data.mendeley.com/oai

oai:data.mendeley.com/k6j32sdgv7.1 2026-08-24T01:08:19Z

jin, zhixiong Bacterial resistance1 Mendeley Data Carbapenem-resistant Enterobacteriaceae (CRE), particularly strains producing New Delhi metallo-β-lactamase-1 (NDM-1), pose a severe global health threat. The SecYEGtranslocon is essential for protein transport across the inner membrane of Gram-negative bacteria, yet its role in β-lactamase secretion under antibiotic stress and its therapeutic potential remain unexplored. Here, we demonstrate that the SecYEG complex serves as the primary translocation channel for NDM-1, CTX-M-9, and TEM-1, and that sub-inhibitory imipenem and cefepime exposure coordinately upregulate both β-lactamase genes (blaNDM-1, blaCTX-M-9, blaTEM-1) and SecYEGtranslocon components (secY, secE, secG) in recombinant E. coli models. This transcriptional co-upregulation correlates with increased β-lactamase activity, enhanced hydrolytic capacity, and the emergence of a multidrug-resistant phenotype, revealing a previously unrecognized adaptive mechanism whereby antibiotic stress potentiates resistance by boosting secretory machinery. Importantly, the natural flavonoid luteolin-7-O-glucoside (LOG) effectively reverses this phenotype-downregulating resistance and translocon gene expression, reducing enzymatic activity, and restoring β-lactam susceptibility. Mechanistically, molecular docking and MST confirmed that LOG binds directly to NDM-1 (Gln123, Lys211, and Asn220)and to specific residues (Ile82, Ile278) on SecY.These findings establish the SecYEGtransloconas a viable, stress-responsive therapeutic target and identify LOG as a first-in-class dual-acting adjuvant that inhibits β-lactamase activity and blocks its SecY-dependent translocation, offering a promising strategy to combat multidrug-resistant CRE infections. Molecular Biology Applied Microbiology Bacterial Structural Biology Dataset doi:10.17632/k6j32sdgv7.1 oai:data.mendeley.com/k6j32sdgv7.1 Creative Commons Attribution 4.0 International http://creativecommons.org/licenses/by/4.0 https://data.mendeley.com/datasets/k6j32sdgv7 2026-08-24T01:08:19Z