PDF(Pubmed)
Abstract：
The widespread dissemination of carbapenem-resistant Klebsiella pneumoniae (CRKP) and its drug resistance transfer poses a global public health threat. While previous studies outlined CRKP\'s drug resistance mechanism, there is limited research on strategies inhibiting CRKP drug resistance spread. This study investigates the potential of Bifidobacterium longum (B. longum) FB1-1, a probiotic, in curbing the spread of drug resistance among CRKP by evaluating its cell-free supernatant (CFS) for antibacterial activity. Evaluating the inhibitory effect of FB1-1 CFS on CRKP drug resistance spread involved analyzing its impact on drug resistance and virulence gene expression; drug resistance plasmid transfer FB1-1 CFS exhibited an MIC range of 125 μL/mL against CRKP. After eight hours of co-culture, CFS achieved a 96% and 100% sterilization rate at two and four times the MIC, respectively. At sub-inhibitory concentrations (1/2× MIC), FB1-1 CFS reduced the expression of the bla_KPC gene, which is pivotal for carbapenem resistance, by up to 62.13% across different CRKP strains. Additionally, it markedly suppressed the expression of the uge gene, a key virulence factor, by up to 91%, and the fim_H gene, essential for bacterial adhesion, by up to 53.4%. Our study primarily focuses on determining the inhibitory effect of FB1-1 CFS on CRKP strains harboring the bla_KPC gene, which is a critical resistance determinant in CRKP. Furthermore, FB1-1 CFS demonstrated the ability to inhibit the transfer of drug resistance plasmids among CRKP strains, thus limiting the horizontal spread of resistance genes. This study highlights FB1-1 CFS\'s inhibitory effect on CRKP drug resistance spread, particularly in strains carrying the bla_KPC gene, thus offering a novel idea and theoretical foundation for developing antibacterial drugs targeting CRKP resistance.
摘要：
耐碳青霉烯类肺炎克雷伯菌（CRKP）的广泛传播及其耐药性转移对全球公共卫生构成威胁。虽然以前的研究概述了CRKP的耐药机制，关于抑制CRKP耐药性传播的策略研究有限。这项研究调查了长双歧杆菌（B.longum)FB1-1，一种益生菌，通过评估其无细胞上清液（CFS）的抗菌活性来抑制CRKP之间耐药性的传播。评估FB1-1CFS对CRKP耐药性传播的抑制作用涉及分析其对耐药性和毒力基因表达的影响；耐药性质粒转移FB1-1CFS对CRKP的MIC范围为125μL/mL。经过八个小时的共同培养，CFS在MIC的2倍和4倍时实现了96％和100％的灭菌率，分别。在亚抑制浓度（1/2×MIC），FB1-1CFS降低了bla_KPC基因的表达，这是耐碳青霉烯的关键，不同CRKP菌株的比例高达62.13%。此外,它显著抑制了uge基因的表达，一个关键的毒力因子,高达91%，还有fim_H基因,细菌粘附所必需的，高达53.4%。我们的研究主要集中在确定FB1-1CFS对携带bla_KPC基因的CRKP菌株的抑制作用，这是CRKP的关键抗性决定因素。此外，FB1-1CFS证明了抑制耐药质粒在CRKP菌株之间转移的能力，从而限制了抗性基因的水平传播。本研究强调了FB1-1CFS对CRKP耐药性传播的抑制作用，特别是在携带bla_KPC基因的菌株中，从而为开发针对CRKP耐药的抗菌药物提供了新的思路和理论基础。
