# Chlamydia trachomatis manipulates (PI)CALM to carry on

> **NIH NIH R21** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2024 · $207,225

## Abstract

PROJECT SUMMARY
The CDC estimates that 10% of women between the ages of 15 to 19 test positive for Chlamydia trachomatis
and 50-70% of these infections are asymptomatic. This increases the risk of widespread transmission and
untreated infections, which can lead to pelvic inflammatory disease or infertility in a significant portion of
women of childbearing age. Hence, there is a great need to identify strategies to reduce/prevent transmission
and limit infections to the primary site of inoculation. Within the host cell, infectious elementary bodies (EBs)
differentiate into non-infectious reticulate bodies (RBs) in a pathogen-specified organelle termed the chlamydial
inclusion. During later stages of chlamydial development that precede egress, RBs will undergo secondary
differentiation to form new EBs. The success of Chlamydia as a pathogen is owed to its obligate intracellular
lifestyle and successful completion of its developmental cycle within the inclusion. The size of the inclusion
enlarges over the course of chlamydial development to accommodate the increased number of organisms and
at later stages, the inclusion can occlude much of the cytoplasm and dislocate organelles to the periphery of
the host cell. Yet, the host cell remains relatively unstressed, which allows Chlamydia to promote a “silent”
infection that does not attract unwanted attention from the host immune system. We hypothesize that one
mechanism of maintaining a silent infection is the multiple pathways from which Chlamydia draw nutrients.
Early in infection, the inclusion will intercept free amino acids from the lysosome and form membrane contact
sites with the endoplasmic reticulum. During mid- to late- cycle, the inclusion intercepts post-Golgi exocytic
vesicles to obtain sphingomyelin and cholesterol and recruits transferrin to the periphery of the inclusion via the
slow-transferrin recycling pathway. A previous study in the laboratory demonstrated that the clathrin adaptor
molecule, PICALM, localizes to the chlamydial inclusion. PICALM plays a central role in maintaining
cholesterol homeostasis and regulates transferrin recycling. siRNA knockdown of PICALM in chlamydial
infected cells increased lipid trafficking and transferrin trafficking to the inclusion. These data suggest that
PICALM may function during chlamydial infection to limit host cell stress by maintaining a balance in nutrient
trafficking within the cell. Current data in the field have linked PICALM to managing trafficking in the trans-
Golgi, as part of its role in recycling pathways. Our data also indicate that PICALM may function in part to
maintain Golgi structure and play a role in intra-Golgi trafficking—a previously undescribed finding. For this
current proposal, we hypothesize that Chlamydia manipulates PICALM activity in the Golgi and slow-transferrin
recycling pathways to support host cell homeostasis. A better understanding of how Chlamydia manipulates
these pathways may be useful towards improving ...

## Key facts

- **NIH application ID:** 10950429
- **Project number:** 1R21AI185536-01
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Elizabeth Ann Rucks
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $207,225
- **Award type:** 1
- **Project period:** 2024-09-04 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10950429

## Citation

> US National Institutes of Health, RePORTER application 10950429, Chlamydia trachomatis manipulates (PI)CALM to carry on (1R21AI185536-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10950429. Licensed CC0.

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