Phage Abp1 Rescues Human Cells and Mice from Infection by Pan-Drug Resistant Acinetobacter Baumannii

Cellular Physiology and Biochemistry

Supeng Yin¹  Guangtao Huang¹  Yizhi Peng¹  Bo You¹  Zhiqiang Yuan¹  Bei Jiang¹  Zichen Yang¹  Zhiwei Dong¹  Yulong Zhang²  Yan Zhao³  Fuquan Hu³ 

[1] a;a,c;b

关键词: A. baumannii;    Phage therapy;    Local infection;    Systemic infection;    HeLa cell;    THP-1 cell;    Cytotoxicity;   

DOI  :  10.1159/000486117

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Background/Aims As an “ESKAPE” pathogen, Acinetobacter baumannii is one of the leading causes of drug-resistant infections in humans. Phage therapy may be a useful strategy in treating infections caused by drug-resistant A. baumannii. Among 21 phage strains that were isolated and described earlier, we investigated the therapeutic efficacy of Abp1 because of its relatively wide host range. Methods Phage stability assays were used to evaluate thermal and pH stability of Abp1. Abp1 was co-cultured with A. baumannii (AB1) over a range of multiplicities of infection to determine its bactericidal efficacy. HeLa or THP-1 cells were used in the cytotoxicity and protection assays. Finally, the therapeutic effects of Abp1 on local and systemic A. baumannii infection in mice were determined. Results We found that Abp1 exhibits high thermal and pH stability and has a low frequency of lysogeny. Bacteriophage resistance also occurs at a very low frequency (3.51±0.46×10^-8), and Abp1 can lyse almost all host cells at a MOI as low as 0.1. Abp1 has no detectable cytotoxicity to HeLa or THP-1 cells as determined by LDH release assay. Abp1 can rescue HeLa cells from A. baumannii infection, even if introduced 2 hours post infection. In both local and systemic A. baumannii infection mouse models, Abp1 treatment exhibits good therapeutic effects. Conclusion Abp1 is an excellent candidate for phage therapy against drug-resistant A. baumannii infections.

【 授权许可】

CC BY-NC-ND