Disruption of zinc homeostasis reverses tigecycline resistance in Klebsiella pneumoniae

The findings of this study pave the way for innovative strategies and approaches in the clinical development of novel antimicrobial agents. By using zinc ionophores such as PBT2 to elevate intracellular zinc ion levels, we can overcome bacterial resistance to antibiotics like tigecycline. The suppression of superoxide dismutase activity and elevation of reactive oxygen species concentration suggest that PBT2 impairs the oxidative stress response of K. pneumoniae, further enhancing its susceptibility to antibiotics. Furthermore, the inhibition of the cell wall synthesis pathway and restriction of the efflux pump mechanism provide additional mechanisms by which PBT2 reverses antibiotic resistance. These results highlight the potential of zinc ionophores as a novel class of antimicrobial agents and warrant further investigation into their clinical applications.