Bacterial resistance1

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.