Fluorescence Polarization-Based High-Throughput Screening Enables Identification of Vibrio β-Lactam Resistance Sensor Kinase Inhibitors to Counteract Antibiotic Resistance.

transcription without affecting bacterial growth but markedly potentiated the activity of β-lactam antibiotics. In a bacteria-challenged zebrafish model, LPZ-51 synergized with carbenicillin to reduce bacterial burden, alleviate intestinal inflammation, and improve host survival. Together, these findings demonstrate that targeting VbrK attenuates β-lactam resistance by blocking β-lactamase induction at the transcriptional level, providing a mechanistically distinct antiresistance strategy complementary to existing β-lactam therapies.