Protective Effects of Recombinant Depolymerase Dep44 Against K64-CRKP-Induced Pulmonary Infection in a Murine Infection Model
Carbapenem-resistant Klebsiella pneumoniae (CRKP), particularly the K64 serotype, poses a severe clinical threat due to its high virulence and multidrug resistance. In this study, we investigated the gene expression profiles of host lung tissues to understand the pathogenesis of K64-CRKP infection and the therapeutic mechanism of Dep44, a capsule-degrading depolymerase. An acute pneumonia mouse model was established via intranasal infection with K64-CRKP. We performed high-throughput RNA sequencing (RNA-seq) on lung tissues from four experimental groups: the negative control group (healthy mice), the positive control group (K64-CRKP infected model), the treatment group (infected mice treated with Dep44), and the drug control group (healthy mice treated with Dep44). The analysis aims to elucidate the host immune response to K64-CRKP infection and evaluate how Dep44 treatment modulates these transcriptomic changes to exert its therapeutic effect. Overall design: Lung tissue samples were collected from BALB/c mice to analyze gene expression changes. The study design included four groups: (1) Negative Control Group: Mice were mock-infected with PBS to serve as a healthy baseline. (2) Positive Control Group (Model): Mice were intranasally infected with K64-CRKP to induce acute pneumonia, serving as the disease model for comparison. (3) Treatment Group: Mice were intranasally infected with K64-CRKP and subsequently treated with Dep44. (4) Drug Control Group: Healthy mice were administered Dep44 alone to evaluate the potential off-target effects of the drug itself. Total RNA was extracted from the lung tissues of each group. Libraries were constructed and subjected to high-throughput sequencing on the Illumina platform to compare the transcriptomic differences among these groups.