# Elucidating how intracellular bacterial pathogens hijack host intercellular communication to promote spread

> **NIH NIH R00** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2020 · $59,958

## Abstract

The goal of the research plan outlined in this proposal is to understand how two bacterial pathogens,
Rickettsia parkeri and Listeria monocytogenes, hijack host pathways of intercellular communication to
promote spread; a process that is crucial for their virulence. These pathogens live in the host cell cytosol and
spread from cell to cell by mobilizing the host’s actin cytoskeleton for intracellular motility and transport to the
plasma membrane. Once at the cell periphery, they induce the formation of membrane protrusions that are
engulfed by neighboring cells. Despite recent advances, we lack critical information about how these stages
of spread occur. Based on my preliminary work, this proposal will investigate the specific hypothesis that
bacterial pathogens promote spread by hijacking proteins normally involved in cell adhesion, membrane
remodeling, and endocytosis; processes critically involved in intercellular communication. Furthermore, I
hypothesize that distinct host pathways are hijacked by each pathogen. I propose the following experiments
to test these hypotheses. In Aim 1, I will identify which endocytic, cell adhesion, and membrane remodeling
proteins specifically promote spread and their mechanisms of action. To provide further mechanistic insight,
in Aim 2 I will utilize live cell imaging to determine the dynamics of host protein recruitment, and super-resolution
imaging to define the subcellular architecture of those host proteins studied in Aim 1. This will
reveal the order in which host proteins are recruited and their spatial organization during spread, providing
key insights into their mechanisms of action. Finally, to examine how bacterial effector proteins hijack host
factors to promote spread, in Aim 3 I will follow-up on the exciting discovery that the R. parkeri secreted
effector Sca4 inhibits the cell adhesion protein vinculin to promote spread. I will investigate how and when
Sca4 is secreted and where it targets vinculin in the host cell. As a whole, this work will delineate how
bacterial effectors and host pathways cooperate to enable spread, and reveal similarities and differences in
the molecular strategies of spread for diverse pathogens. Discerning the targets of spread should also
improve our understanding of basic cellular mechanisms, like vesicular traffic and intercellular
communication, and how these go awry in disease.

## Key facts

- **NIH application ID:** 10072478
- **Project number:** 3R00GM115765-05S1
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** REBECCA L LAMASON
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $59,958
- **Award type:** 3
- **Project period:** 2015-09-01 → 2020-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10072478

## Citation

> US National Institutes of Health, RePORTER application 10072478, Elucidating how intracellular bacterial pathogens hijack host intercellular communication to promote spread (3R00GM115765-05S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10072478. Licensed CC0.

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