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Nanobody Mediated Neutralization of Listeria monocytogenes
Author(s) -
Brooks Cory,
Huh Ian,
Toride Moeko,
Shenai Akhelish
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.912.11
Subject(s) - listeria , listeria monocytogenes , microbiology and biotechnology , endocytosis , biology , listeria infection , antibody , virulence , receptor , immunology , bacteria , genetics , gene
Listeriosis represents a significant public health concern, as consumption of food contaminated with Listeria monocytogenes can result in fatal meningitis and termination of the fetus during pregnancy. A series of recent outbreaks originating from foods historically considered to be low risk for Listeria infection highlights the need for novel strategies to improve food safety. The first step in bacterial invasion of host cells is interaction of Listeria cell surface proteins called Internalins with host cell receptors triggering receptor‐mediated endocytosis. Internalin B (InlB) binds the receptor tyrosine kinase cMET, an interaction that has been demonstrated to be crucial for bacterial invasion of the placenta. Given the importance of this interaction for bacterial virulence it represents a target for therapeutic intervention. We have isolated several nanobodies, the single domain antibodies derived from the unique heavy‐chain antibodies of camels, which bind to InlB with high affinity. A combination of gentamicin protection assays and florescent microscopy demonstrate that InlB specific nanobodes can block the invasion of Listeria cell in vitro . Furthermore, a high resolution X‐ray structure of one of the nanobodies in complex with InlB reveals that the nanobody binds the cMet interaction site, acting as a competitive inhibitor preventing bacterial invasion. The results presented point to the potential of nanobodies as a novel class of therapeutics for the prevention of Listeriosis. Support or Funding Information Projected is funded by a NIH SCORE (SC3) grant (SC3GM112532)