Microbiome Therapeutic Lactiplantibacillus plantarum PMC105 for Systemic Carbapenem-Resistant Enterobacteriaceae Infections: Oral and Inhalation Efficacy In Vivo
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Carbapenem-resistant Enterobacteriaceae (CRE), particularly Klebsiella pneumoniae, are major causes of severe systemic infections due to their resistance to most antibiotics and the high associated mortality, representing a growing global health concern. In this study, we report the in vivo efficacy of a novel probiotic strain, Lactiplantibacillus plantarum PMC105, against systemic CRE infections. In a mouse model characterized by neutropenia and antibiotic-induced gut dysbiosis, infection with carbapenem-resistant K. pneumoniae (CRKP) resulted in 60% mortality within two weeks. However, oral administration of PMC105 significantly reduced intestinal CRKP colonization, minimized body weight loss, and resulted in 100% survival. This therapeutic effect is presumed to result from enhanced gut barrier function, driven by upregulation of the tight junction protein ZO-1 in the ileum, thereby preventing bacterial translocation and subsequent systemic dissemination. In a therapeutic model of systemic infection following translocation, intranasal administration of PMC105 reduced bacterial loads in the stool, liver, kidneys, and lungs, improved clinical symptoms, and maintained body weight, thereby increasing survival rates. Comprehensive safety evaluations, including antibiotic susceptibility testing, hemolysis, bile salt deconjugation, D-lactate production, and cytotoxicity assays, confirmed the strain's safety. These findings support the potential of PMC105 as a dual-route microbiome-based therapeutic candidate for the treatment of systemic CRE infections and warrant further clinical investigation.
Abstract
Carbapenem-resistant Enterobacteriaceae (CRE), particularly Klebsiella pneumoniae, are major causes of severe systemic infections due to their resistance to most antibiotics and the high associated mortality, representing a growing global health concern. In this study, we report the in vivo efficacy of a novel probiotic strain, Lactiplantibacillus plantarum PMC105, against systemic CRE infections. In a mouse model characterized by neutropenia and antibiotic-induced gut dysbiosis, infection with carbapenem-resistant K. pneumoniae (CRKP) resulted in 60% mortality within two weeks. However, oral administration of PMC105 significantly reduced intestinal CRKP colonization, minimized body weight loss, and resulted in 100% survival. This therapeutic effect is presumed to result from enhanced gut barrier function, driven by upregulation of the tight junction protein ZO-1 in the ileum, thereby preventing bacterial translocation and subsequent systemic dissemination. In a therapeutic model of systemic infection following translocation, intranasal administration of PMC105 reduced bacterial loads in the stool, liver, kidneys, and lungs, improved clinical symptoms, and maintained body weight, thereby increasing survival rates. Comprehensive safety evaluations, including antibiotic susceptibility testing, hemolysis, bile salt deconjugation, D-lactate production, and cytotoxicity assays, confirmed the strain's safety. These findings support the potential of PMC105 as a dual-route microbiome-based therapeutic candidate for the treatment of systemic CRE infections and warrant further clinical investigation.