AI Article Synopsis
- The study addresses the growing issue of Carbapenem-resistant Klebsiella pneumoniae (CRKP) linked to the blaNDM-1 gene in hospital-acquired pneumonia (HAP) and looks into how its expression can be controlled.
- Significant findings showed that CRKP strains had increased blaNDM-1 expression identified through RNA sequencing, and using CRISPR-Cas9 to delete this gene restored bacterial sensitivity to antibiotics.
- Combining Imipenem with other treatments like Thanatin or Subactam improved the effectiveness against CRKP, highlighting strategies to combat antibiotic resistance.
Article Abstract
Background: The escalating challenge of Carbapenem-resistant Klebsiella pneumoniae (CRKP) in hospital-acquired pneumonia (HAP) is closely linked to the blaNDM-1 gene. This study explores the regulatory mechanisms of blaNDM-1 expression and aims to enhance antibacterial tactics to counteract the spread and infection of resistant bacteria.
Methods: KP and CRKP strains were isolated from HAP patients' blood samples. Transcriptomic sequencing (RNA-seq) identified significant upregulation of blaNDM-1 gene expression in CRKP strains. Bioinformatics analysis revealed blaNDM-1 gene involvement in beta-lactam resistance pathways. CRISPR-Cas9 was used to delete the blaNDM-1 gene, restoring sensitivity. In vitro and in vivo experiments demonstrated enhanced efficacy with Imipenem and Thanatin or Subatan combination therapy.
Results: KP and CRKP strains were isolated with significant upregulation of blaNDM-1 in CRKP strains identified by RNA-seq. The Beta-lactam resistance pathway was implicated in bioinformatics analysis. Knockout of blaNDM-1 reinstated sensitivity in CRKP strains. Further, co-treatment with Imipenem, Thanatin, or Subactam markedly improved antimicrobial effectiveness.
Conclusion: Silencing blaNDM-1 in CRKP strains from HAP patients weakens their Carbapenem resistance and optimizes antibacterial strategies. These results provide new theoretical insights and practical methods for treating resistant bacterial infections.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10893750 | PMC |
| http://dx.doi.org/10.1186/s10020-024-00794-y | DOI Listing |
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