Intracellular Zn²⁺ dynamics regulate cefiderocol resistance in Klebsiella pneumoniae - PubMed
4 days ago
- #Cefiderocol
- #NDM
- #Zn²�� dynamics
- Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a global threat, especially strains producing New Delhi metallo-β-lactamase (NDM).
- NDM-producing K. pneumoniae show high resistance to cefiderocol, a siderophore antibiotic.
- Oxidative stress under host nutritional immunity and cefiderocol exposure leads to rapid increases in intracellular Zn²�� concentrations.
- Increased Zn²�� levels enhance NDM enzyme activity, contributing to high cefiderocol resistance.
- The gene JNMCOFLA_01041 is crucial for Zn²�� and hemin absorption, affecting oxidative stress resistance, NDM activity, metabolism, and pathogenicity.
- Dynamic changes in bacterial metal ion concentrations under host conditions impact survival and drug resistance.
- Monitoring and regulating bacterial internal environment changes during antimicrobial use is essential for efficacy.
- JNMCOFLA_01041 is a potential target for novel drugs and vaccines.