# Mechanism of RB-to-EB Conversion in Chlamydia

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2020 · $653,583

## Abstract

Project Summary/Abstract
 Chlamydia genital infections are the most commonly reported infection in the U.S. All
Chlamydia species cause an unusual intracellular infection in which there is conversion
between a dividing form of the bacterium (reticulate body or RB) and the infectious form
(elementary body or EB). RB-to-EB conversion is critical for producing infectious
progeny that can spread the infection to a new host cell, but the mechanisms that
regulate it are unknown. There has been a longstanding assumption in the Chlamydia
field that conversion is regulated by an extrinsic factor. However, we have obtained data
to support a new regulatory mechanism in which RB size is used as an intrinsic factor to
control conversion. Based on temporal measurements of chlamydial size and number
obtained with three-dimensional electron microscopy (3D EM), we hypothesize that RBs
undergo size reduction through successive rounds of replication and can only convert
into an EB below a size threshold. In Aim 1, we will test this size control mechanism by
determining whether RB size is altered when the timing of RB-to-EB conversion onset is
changed. In Aim 2, we will investigate if the size of the first RB plays a role in starting
the timer of RB size reduction that eventually culminates in RB-to-EB conversion. In Aim
3, we will study how RB size could be used to regulate conversion. We propose a
titration mechanism in which EUO, a repressor of late chlamydial genes, is titrated away
in smaller RBs to promote conversion. In Aim 4, we will study alternative mechanisms
that utilize extrinsic signals to control conversion. Using mathematical modeling and 3D
EM analysis, we will test a contact-dependent mechanism, which is based on contact of
the RB with the inclusion membrane as the external signal, and a chlamydial
communication mechanism in which the external signal is produced by other
chlamydiae. These studies will provide important information about the mechanism of
RB-to-EB conversion that can be applied in new therapeutic strategies to block the
developmental cycle and the production of infectious progeny.

## Key facts

- **NIH application ID:** 9947284
- **Project number:** 1R01AI151212-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Daniela Boassa
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $653,583
- **Award type:** 1
- **Project period:** 2020-02-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9947284

## Citation

> US National Institutes of Health, RePORTER application 9947284, Mechanism of RB-to-EB Conversion in Chlamydia (1R01AI151212-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9947284. Licensed CC0.

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