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

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

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

محل انتشار: مجله علوم پایه پزشکی ایران، دوره: 25، شماره: 9

سال انتشار: 1401

نوع سند: مقاله ژورنالی

زبان: انگلیسی

مشاهده: 166

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https://civilica.com/doc/1513838

شناسه ملی سند علمی:

JR_IJBMS-25-9_014

تاریخ نمایه سازی: 20 شهریور 1401

چکیده مقاله:

Objective(s): The high resistance rate of Acinetobacter baumannii and the limited number of available antibiotics have prompted a worldwide effort to develop effective antimicrobial agents. Accordingly, identifying single-chain variable fragment antibodies (scFvs), capable of exerting direct antibacterial activity in an immune system-independent manner, may be making immunocompromised patients more susceptible to A. baumannii infections.Materials and 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, EB۲۱۱ and EB۲۷۹, 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 EB۲۱۱, EB۲۷۹, or a cocktail of EB۲۱۱ and EB۲۷۹ (۲۰۰ µg/ml), displayed lower viability (approximately ۵۰%, ۷۸%, and ۴۰% viability, respectively) compared with PBS-treated bacteria.Conclusion: These results suggest that combining last-resort antibiotics with bactericidal scFvs could provide promising outcomes in immunocompromised individuals with A. baumannii infections.

کلیدواژه ها:

Acinetobacter baumannii ، Antibacterial agents ، Colistin ، Monoclonal antibody ، Phage display library ، Single-chain variable-fragment

نویسندگان

Eilnaz Basardeh