Chimeric hBPI23-Fcγ protein shows bactericidal activity against drug-resistant Gram-negative bacteria and protects mice from lethal challenge

IF 2.3 3区生物学 Q3 MICROBIOLOGY

Archives of Microbiology Pub Date : 2025-03-28 DOI:10.1007/s00203-025-04306-2

Tianxiao Ma, Yang Wang, Chaoben Huang, Xulong Zhang, Yunqing An, Qi Zhang, Qingli Kong, Bin Cao

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Abstract

The antimicrobial peptides, such as host immune system-derived human bactericidal/permeability-increasing protein (hBPI), are the potential drugs for antibiotic-resistant Gram-negative bacterial infection. However, whether the purified chimeric hBPI₂₃-Fcγ protein has bactericidal activity against drug-resistant Gram-negative bacteria (GNB) and the relevant mechanisms have not been fully elucidated. In this study, the chimeric hBPI₂₃-Fcγ protein, which consisting of the functional N terminus of BPI and Fcγ1, were expressed and purified in a lab-scale. The chimeric hBPI₂₃-Fcγ protein showed longer half-life up to 148.2 min in vivo. The hBPI₂₃-Fcγ protein also showed significant bactericidal activity against standard and clinically isolated drug-resistant Acinetobacter baumannii (A. baumannii) and Escherichia coli (E. coli). In addition, the hBPI₂₃-Fcγ protein markedly decreased biofilm formation, neutralized bacterial lipopolysaccharides (endotoxin) and enhanced the opsonization of phagocytes, as well as significantly improved the survival rate of minimal lethal dose (MLD) of drug-resistant E. coli -infected mice. These results indicate that the BPI₂₃-Fcγ protein protected mice from drug-resistant GNB infection not only by direct bactericidal effect, but also by promoting opsonophagocytosis of macrophages. In conclusion, the chimeric BPI₂₃-Fcγ protein may be as a promising candidate of non-antibiotic biological agent for drug-resistant GNB infection.

Graphical Abstract

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嵌合hBPI23-Fcγ蛋白对耐药革兰氏阴性菌具有杀菌活性，可保护小鼠免受致命攻击

宿主免疫系统源性人杀菌/通透性增加蛋白（hBPI）等抗菌肽是耐药革兰氏阴性菌感染的潜在药物。然而，纯化的嵌合hBPI23-Fcγ蛋白是否具有对耐药革兰氏阴性菌（GNB）的杀菌活性及其机制尚不完全清楚。本研究在实验室规模下表达并纯化了由BPI和Fcγ1的功能N端组成的嵌合hBPI23-Fcγ蛋白。嵌合hBPI23-Fcγ蛋白在体内的半衰期可达148.2 min。hBPI23-Fcγ蛋白对标准和临床分离的耐药鲍曼不动杆菌（A. baumannii）和大肠杆菌（E. coli）也显示出显著的杀菌活性。此外，hBPI23-Fcγ蛋白显著减少生物膜的形成，中和细菌脂多糖（内毒素），增强吞噬细胞的调节作用，并显著提高耐药大肠杆菌感染小鼠的最小致死剂量（MLD）存活率。这些结果表明，BPI23-Fcγ蛋白保护小鼠免受耐药GNB感染不仅通过直接杀菌作用，而且通过促进巨噬细胞的调理吞噬作用。综上所述，嵌合BPI23-Fcγ蛋白可能是耐药GNB感染的一种有前景的非抗生素生物制剂。图形抽象

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来源期刊

Archives of Microbiology 生物-微生物学

CiteScore

4.90

自引率

3.60%

发文量

601

审稿时长

3 months

期刊介绍： Research papers must make a significant and original contribution to microbiology and be of interest to a broad readership. The results of any experimental approach that meets these objectives are welcome, particularly biochemical, molecular genetic, physiological, and/or physical investigations into microbial cells and their interactions with their environments, including their eukaryotic hosts. Mini-reviews in areas of special topical interest and papers on medical microbiology, ecology and systematics, including description of novel taxa, are also published. Theoretical papers and those that report on the analysis or ''mining'' of data are acceptable in principle if new information, interpretations, or hypotheses emerge.