Two Novel Single-Chain Variable Fragments, EB211 and EB279, Exert Antibacterial Activity Against Acinetobacter baumannii by Destabilizing the Outer Membrane
Introduction: Acinetobacter baumannii is notorious for its high resistance levels, and the development of clinically effective antimicrobial agents is an urgent medical challenge. Single-chain variable fragments (scFvs) that exhibit antibacterial properties against challenging pathogens, such as...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Pasteur Institute of Iran
2024-12-01
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| Series: | Journal of Medical Microbiology and Infectious Diseases |
| Subjects: | |
| Online Access: | https://jommid.pasteur.ac.ir/article-1-678-en.html |
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| Summary: | Introduction: Acinetobacter baumannii is notorious for its high resistance
levels, and the development of clinically effective antimicrobial agents is an
urgent medical challenge. Single-chain variable fragments (scFvs) that
exhibit antibacterial properties against challenging pathogens, such as
Pseudomonas aeruginosa and Staphylococcus aureus, have the potential to
improve therapeutic strategies significantly. Their unique ability to function
independently of the host immune system makes scFvs a highly promising
option for effective treatment. In our previous studies, we identified two
human scFvs (EB211 and EB279) that showed direct growth inhibition
activity against A. baumannii strains in vitro and therapeutic effectiveness in
immunocompromised mice with pneumonia caused by an extensively drugresistant
A. baumannii strain. In the present study, we endeavored to
demonstrate how EB211 and EB279 could inhibit the growth of A.
baumannii. Methods: A. baumannii, Klebsiella pneumoniae, and
Pseudomonas aeruginosa strains were individually incubated with the scFv
in the presence of a high concentration of magnesium (MgSO4; 20 mM).
Epitope mapping and immunoblotting were conducted to identify A.
baumannii proteins likely bound by EB211 and EB279. Results: It was
found that EB211 and EB279, similar to colistin sulfate, lost their activity in
the presence of magnesium. Moreover, immunoblotting revealed that EB211
and EB279 might bind the OprD family outer membrane porin and TonB
family C-terminal domain protein, respectively. Conclusion: EB211 and
EB279 elicit direct growth inhibitory activity against A. baumannii without
needing immune cells or complements, which could be helpful for
immunocompromised patients. |
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| ISSN: | 2345-5349 2345-5330 |