Researchers at Anhui Medical University have developed inhalable microspheres that combine meropenem with cobalt ions to treat drug-resistant carbapenem-resistant Klebsiella pneumoniae (CRKP) pneumonia, according to a study published in Nature Communications. The microspheres, designated SCM, are fabricated using microfluidics by cross-linking sodium alginate with cobalt ions.
The treatment addresses carbapenem resistance through a dual-action mechanism mediated by cobalt ions. In metallo-beta-lactamase NDM-1 strains, cobalt ions irreversibly inhibit the enzyme by displacing zinc ions from its active site, which restores the bactericidal activity of meropenem. In serine-mediated KPC-2-producing strains, the cobalt ions disrupt bacterial iron and sulfur metabolism, forcing the bacteria into energy starvation and inefficient fermentation.
In laboratory tests, SCM demonstrated potent in vitro activity against target bacterial strains and disrupted established biofilms. Testing in mouse models revealed that inhaling the microspheres lowered bacterial loads in lung tissue, raised survival rates, and decreased inflammatory damage while regulating lung immune responses.
The therapy altered several cellular immune pathways in infected mice. Inhaled SCM limited excessive neutrophil migration to the lungs, inhibited M1 macrophage polarization while encouraging conversion to the M2 phenotype, reversed T-cell exhaustion, and preserved natural killer cell homeostasis. Transcriptomic analysis of lung tissue showed that the treatment reversed infection-induced genetic dysregulation and upregulated genes associated with tissue repair.
Zhaoyou Chu, Jun Liang, and Yayun Wu contributed equally to the study, working alongside co-authors Ling Xu, Hanqing Zhang, Jiyang Wang, Min Shao, and Haisheng Qian across Anhui Medical University's School of Biomedical Engineering, Department of Critical Care Medicine, and School of Pharmaceutical Sciences. Funding for the research was provided by the National Natural Science Foundation of China, the China Postdoctoral Science Foundation, and the Scientific Research Project of Anhui Provincial Department of Education.
