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

摘要

biBackground/Aims/i/b As an “ESKAPE” pathogen, iAcinetobacter baumannii/i 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 iA. baumannii/i. Among 21 phage strains that were isolated and described earlier, we investigated the therapeutic efficacy of Abp1 because of its relatively wide host range. biMethods/i/b Phage stability assays were used to evaluate thermal and pH stability of Abp1. Abp1 was co-cultured with iA. baumannii/i (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 iA. baumannii/i infection in mice were determined. biResults/i/b 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±0.46×10sup-8/sup), 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 iA. baumannii/i infection, even if introduced 2 hours post infection. In both local and systemic iA. baumannii/i infection mouse models, Abp1 treatment exhibits good therapeutic effects. biConclusion/i/b Abp1 is an excellent candidate for phage therapy against drug-resistant iA. baumannii/i infections.