Klebsiella pneumoniae Genome sequencing and assembly
The antimicrobial potency of zinc is attributed to its capacity to compromise bacterial structure and protein functionality, thereby achieving the inhibition and eradication of bacteria. However, despite its antimicrobial prowess, bacteria have developed a variety of mechanisms to expel excess zinc ions from their cells. This evolutionary advancement has allowed numerous bacteria to thrive in environments rich in metal ions at high concentrations, thereby circumscribing the clinical application of metal ions as antimicrobial agents.In this study, we employed the zinc ionophore PBT2 to elevate intracellular zinc ion levels in Klebsiella pneumoniae and discovered that PBT2 reversed the resistance of Klebsiella pneumoniae to tigecycline. Our research indicates that PBT2 can increase the concentration of intracellular zinc ions in K. pneumoniae, suppress the activity of superoxide dismutase within the cell, and elevate the concentration of reactive oxygen species within the bacterial cell, thus impairing the oxidative stress response. Concurrently, the disruption of zinc homeostasis significantly inhibits the cell wall synthesis pathway in Klebsiella pneumoniae, potentially restricting the efflux pump mechanism that predominantly drives tigecycline resistance to some extent. This discovery paves the way for innovative strategies and approaches in the clinical development of novel antimicrobial agents in the future.