Allicin Targets Carbapenemase and Efflux Pump Activity in Klebsiella pneumoniae to Mitigate Meropenem Resistance.

Abstract

Antimicrobial resistance in Klebsiella pneumoniae (KP) has become a major global public health threat. Allicin, a natural antimicrobial agent, has demonstrated antibacterial activity against KP, but its effect on drug resistance remains unclear. To investigate whether allicin can weaken KP's resistance to meropenem (MEM) and reveal its synergistic mechanism, this study treated KP strains with gradient concentrations of MEM. Resistant strains were identified using the broth microdilution method and viable bacterial counting. Checkerboard assay, time-kill kinetics and isobologram analyses were used to analyse the antibacterial effect of different concentrations of allicin and MEM combined treatment. Molecular docking and cellular thermal shift assay (CETSA) were employed to evaluate the binding of allicin to carbapenemase and efflux pump-related proteins. A mouse model of KP pneumonia was established to investigate the therapeutic effect of allicin combined with MEM. Compared with MEM monotherapy, allicin + MEM acted synergistically, lowering the effective MEM dose by targeting carbapenemase and efflux pumps and mitigating KP-induced pneumonia. This study suggests that the combination of allicin and MEM may be a potential method for reducing bacterial resistance and exerting antibacterial efficacy.