# Deciphering mechanisms of Listeria placental-fetal invasion

> **NIH NIH R56** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2021 · $391,795

## Abstract

Project Summary
Listeria monocytogenes (Lm) is a gram-positive food-borne intracellular bacterial pathogen that is
capable of causing serious invasive disease in humans. As a widespread environmental organism,
Lm is a frequent contaminant of food processing facilities and has been responsible for some of the
largest, most expensive, and most deadly food recalls in US history. Lm is one of a select number of
pathogens that is transmitted during pregnancy from mother to fetus. These infections can be
devastating, as often an infected woman does not even realize she has been infected with Lm until
she miscarries or gives birth to a stillborn or systemically infected infant. The high mortality rate and
devastating sequelae that accompany Lm invasive disease despite antibiotic treatment underlie the
critical need for new therapeutic strategies to safely and effectively manage Lm invasive infections.
We have recently discovered that select isolates of Lm have an enhanced ability to target the placenta
and fetus based on increased expression of the bacterial surface protein InlB. Increased InlB is
sufficient to transform a strain that normally exhibits a low frequency of fetal colonization to a strain
that is capable off nearly 100% fetal infection. Naturally occurring amino acid variations within InlB
may both increase protein stability and enhance stimulation of c-Met, the host growth factor receptor
bound by InlB. Met is abundantly expressed by placental tissue and is required for embryonic and
placental development. We hypothesize that Lm strains expressing select variants of InlB exhibit
enhanced invasion through the manipulation of c-Met signaling pathways, leading to increased rates
of fetal transmission. These strains additionally stimulate a robust immune response that leads to
placental barrier dysfunction and fetal death. The specific aims of this proposal will undertake a
functional assessment of Lm InlB to reveal molecular mechanisms underlying vertical transmission as
well as examine the contributions of maternal and fetal immune signaling to pregnancy outcome. Aim
1 will functionally define the mechanisms underlying InlB surface localization and activity. This aim will
define mechanisms that contribute to InlB stability at the bacterial cell surface and will examine
functional differences between surface localization and secretion. Aim 2 will decipher the mechanisms
underlying InlB enhancement of Lm vertical transmission. We will examine and compare portals of Lm
entry in pregnant mice, and explore host responses to Lm infection that influence pregnancy outcome.
Aim 3 will explore maternal and fetal defenses triggered by high efficiency vertically transmitted
strains that contribute to pathology. These studies will clarify how select Lm isolates gain access with
high efficiency to placental/fetal tissues to cause devastating forms of neonatal disease and death.

## Key facts

- **NIH application ID:** 10436619
- **Project number:** 1R56AI160777-01
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Nancy Elizabeth Freitag
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $391,795
- **Award type:** 1
- **Project period:** 2021-07-14 → 2022-06-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10436619

## Citation

> US National Institutes of Health, RePORTER application 10436619, Deciphering mechanisms of Listeria placental-fetal invasion (1R56AI160777-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10436619. Licensed CC0.

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