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.
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We thank all individuals who participated in this study.
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This work was supported by Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS 2021-I2M-1-048) and Medical Innovation Capacity Enhancement Special Program of Capital Medical University (CXZX 202308).
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The study was designed by QK, YA, and BC. Experiments were performed by TM, YW, CH, and QK. Results were analyzed by TM, XZ and QK. TM, XZ, YA and QK wrote the paper. All authors read and revised the paper. All authors contributed to the article and approved the submitted version.
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Communicated by Mehak Khan.
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Ma, T., Wang, Y., Huang, C. et al. Chimeric hBPI23-Fcγ protein shows bactericidal activity against drug-resistant Gram-negative bacteria and protects mice from lethal challenge. Arch Microbiol 207, 103 (2025). https://doi.org/10.1007/s00203-025-04306-2
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DOI: https://doi.org/10.1007/s00203-025-04306-2