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

  • سال انتشار: 1401
  • محل انتشار: مجله علوم پایه پزشکی ایران، دوره: 25، شماره: 9
  • کد COI اختصاصی: JR_IJBMS-25-9_014
  • زبان مقاله: انگلیسی
  • تعداد مشاهده: 171
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نویسندگان

Eilnaz Basardeh

Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran

Somayeh Piri-Gavgani

Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran

Behnoush Soltanmohammadi

Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran

Mostafa Ghanei

Chemical Injuries Research Center, Systems Biology and Poisoning Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran

Mir Davood Omrani

Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Mahdieh Soezi

Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran

Mohammad Ali Shokrgozar

National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, Iran

Masoumeh Azizi

Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran

Abolfazl Fateh

Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran

Farzam Vaziri

Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran

Seyed Davar Siadat

Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran

Zahra Sharifzadeh

Department of Immunology, Pasteur Institute of Iran, Tehran, Iran

Fatemeh Rahimi-Jamnani

Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran

چکیده

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

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