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The Bacterial Surface Protein Internalin B Enhances Vertical Transmission of Listeria monocytogenes

thesis
posted on 01.05.2020, 00:00 by Nicole Lamond
Listeria monocytogenes is a facultative gram-positive intracellular bacterium that is capable of causing serious invasive infections in pregnant women resulting in abortion, still-birth, and disseminated fetal infection. Previously, a clinical L. monocytogenes isolate, 07PF0776, was identified as having an enhanced ability to target cardiac tissue; this tissue tropism appeared to result from amino acid variations within Internalin B (InlB), a bacterial surface protein associated with host cell invasion. Given that the mammalian receptor bound by InlB, Met, is abundantly expressed by placental tissue, we assessed 07PF0776 for its ability to be transmitted from mother to fetus. Pregnant Swiss-Webster mice were infected on gestational day E13 via tail vein injection with the standard isolate 10403S, a non-cardiotropic strain, or 07PF0776, the cardiac isolate. Pregnant mice infected with 07PF0776 exhibited significantly enhanced transmission of L. monocytogenes to placentas and fetuses compared to 10403S. Both bacterial burdens and the frequency of placental and fetal infection were increased in mice infected with the cardiac isolate. Strain 07PF0776 also exhibited an enhanced ability to invade Jar human trophoblast tissue culture cells in comparison to 10403S. 07PF0776 was found to have increased levels of InlB associated with the bacterial cell surface in comparison to 10403S. Overexpression of surface InlB via genetic modification was sufficient to confer enhanced invasion of the placenta and fetus for both 10403S and 07PF0776. 07PF0776 also exhibited more rapid invasion of the placenta compared to 10403S, with increased bacterial burdens and frequency of infection established as early as 48 hours post infection. 07PF0776 expressing inlB from 10403S (07PF0776 InlBNC) exhibited increased infection of the placenta and fetus compared to 10403S expressing inlB from 07PF0776 (10403S InlBC). It was found that 10403S InlBC did not retain InlB on the bacterial cell surface. These data support a critical role for surface InlB in the vertical transmission of L. monocytogenes.

History

Advisor

Freitag, Nancy

Chair

Freitag, Nancy

Department

Microbiology and Immunology

Degree Grantor

University of Illinois at Chicago

Degree Level

Doctoral

Degree name

PhD, Doctor of Philosophy

Committee Member

Federle, Michael Shukla, Deepak Behnsen, Judith Jeong, Young

Submitted date

May 2020

Thesis type

application/pdf

Language

en

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