# Functional characterization of Chlamydia trachomatis inclusion membrane proteins and their role in subversion of host vesicular trafficking

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2021 · $74,315

## Abstract

Project Summary
Chlamydia trachomatis (C.t.) is the leading cause of non-congenital blindness and the most prevalent sexually
transmitted bacterial infection in the world and thus, has a major impact on global health. C.t. replicates in a
membrane-bound vacuole, termed the inclusion, that is extensively modified early in infection through the
incorporation of over 50 type III secreted effector proteins termed inclusion membrane proteins (Incs). From
within the confines of the inclusion, the bacterium must engage select host organelles to obtain key nutrients
such as lipids and iron for bacterial replication and inclusion expansion. Despite the importance of nutrient
acquisition to chlamydial infection, a major gap in our knowledge exists regarding how C.t. acquires these
essential substrates from the host cell. Recent work from our group shows that the Inc protein CT229 binds and
recruits Rab GTPases and specific Rab effectors to the inclusion. Using cutting-edge genetics, we showed that
the absence of CT229 results in defects in intracellular replication and inclusion development. We hypothesize
that CT229-Rab interactions direct post-Golgi vesicles and recycling endosomes to the inclusion for the
acquisition of essential substrates needed for proliferation and inclusion expansion. In Aim 1, we will determine
how CT229-Rab interactions promote lipid acquisition by hijacking host vesicular trafficking pathways and iron
acquisition by promoting the recruitment of transferrin-positive vesicles to the inclusion. We will evaluate the lipid
composition of the bacterial and inclusion membranes and evaluate the importance of lipid acquisition for
incorporation into the inclusion and bacterial membranes. We will also answer a major long-standing question in
the field by determining whether transferrin indeed serves as a major source of iron for chlamydia and
furthermore mechanistically probe the mechanisms by which chlamydia may extract iron from this pathway. It is
unlikely that CT229 alone controls vesicle hijacking from start to finish, therefore in Aim 2 we will identify the
complex of host and bacterial proteins that are formed at the inclusion during CT229-Rab interactions. Using
cellular, genetic, and molecular techniques we will evaluate the impact of Inc-Inc interactions on Rab-dependent
vesicle transport to the inclusion. Detailed characterization of the bacterial and host proteins that co-opt host
vesicular trafficking during C.t. infection will provide a holistic view of how intracellular pathogens coordinate the
capture and fusion of host vesicles that are necessary for bacterial infection.

## Key facts

- **NIH application ID:** 10394158
- **Project number:** 3R01AI150812-02S1
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Mary Weber
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $74,315
- **Award type:** 3
- **Project period:** 2020-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10394158

## Citation

> US National Institutes of Health, RePORTER application 10394158, Functional characterization of Chlamydia trachomatis inclusion membrane proteins and their role in subversion of host vesicular trafficking (3R01AI150812-02S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10394158. Licensed CC0.

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