Anti- Acinetobacter baumannii single-chain variable fragments show direct bactericidal activity

抗鲍曼不动杆菌单链可变片段表现出直接杀菌活性

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作者:Eilnaz Basardeh, Somayeh Piri-Gavgani, Behnoush Soltanmohammadi, Mostafa Ghanei, Mir Davood Omrani, Mahdieh Soezi, Mohammad Ali Shokrgozar, Masoumeh Azizi, Abolfazl Fateh, Farzam Vaziri, Seyed Davar Siadat, Zahra Sharifzadeh, Fatemeh Rahimi-Jamnani

Conclusion

These results suggest that combining last-resort antibiotics with bactericidal scFvs could provide promising outcomes in immunocompromised individuals with A. baumannii infections.

Methods

To isolate bactericidal scFvs targeting A. baumannii, we panned a large human scFv phage display library against whole-cell extensively drug-resistant (XDR) A. baumannii strains grown as biofilm or cultured with human blood or human peripheral blood mononuclear cells plus plasma. The binding of scFv-phages to A. baumannii was assessed by the dot-blot assay. Soluble scFvs, derived from the selected phages, were assessed based on their ability to bind and inhibit the growth of A. baumannii.

Results

Five phage clones showed the highest reactivity toward A. baumannii. Among five soluble scFvs, derived from positive phage clones, two scFvs, EB211 and EB279, had high expression yields and displayed strong binding to A. baumannii compared with the controls. Moreover, XDR A. baumannii strains treated with positively-charged scFvs, including EB211, EB279, or a cocktail of EB211 and EB279 (200 µg/ml), displayed lower viability (approximately 50%, 78%, and 40% viability, respectively) compared with PBS-treated bacteria.

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