Inhibition of Francisella tularensis phagocytosis using a novel anti-LPS scFv antibody fragment

Scientific Reports
Adva MechalyOhad Mazor

Abstract

Francisella tularensis (Ft), the causative agent of lethal tularemia, is classified as a category A biological warfare threat agent. While Ft infection is treatable by antibiotics, many failed antibiotic treatments were reported, highlighting the need for effective new treatments. It has been demonstrated that binding of antibody-coated bacteria to the Fc receptor located on phagocytic cells is a key process needed for efficient protection against Ft. Yet, Ft utilizes the same receptor to enter the phagocytic cells in order to escape the immune system. To address the question whether an anti-Ft LPS antibody lacking the ability to bind the Fc receptor may inhibit the entry of Ft into host cells, a soluble scFv (TL1-scFv) was constructed from an anti Ft-LPS antibody (TL1) that was isolated from an immune single-chain (scFv) phage-display library. Bacterial uptake was assessed upon infection of macrophages with Ft live attenuated strain (LVS) in the presence of either TL1 or TL1-scFv. While incubation of LVS in the presence of TL1 greatly enhanced bacterial uptake, LVS uptake was significantly inhibited in the presence of TL1-scFv. These results prompt further experiments probing the therapeutic efficacy of TL1-scFv, alone or in c...Continue Reading

References

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Citations

Jul 27, 2021·Frontiers in Cellular and Infection Microbiology·Kristian Daniel Ralph RothMichael Hust
Aug 25, 2021·Critical Reviews in Microbiology·Paulina ŚliwkaAneta Skaradzińska
Sep 23, 2021·Expert Review of Vaccines·Henderson ZhuAndrew J Pollard

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Methods Mentioned

BETA
phage-display
ELISA
biolayer interferometry
biolayer
biosensor
confocal microscopy
transfection

Software Mentioned

GraphPad
Prism
Octet

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