# Defining the persistence associated transcriptome in Chlamydia trachomatis

> **NIH NIH F31** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2022 · $35,525

## Abstract

Project Summary
Chlamydia trachomatis is a Gram-negative, obligate intracellular bacterium that continues to be the world’s most
common bacterial sexually transmitted infection year after year. A combination of a high rate of asymptomatic
cases, resistance to natural clearance, and slow progress in the development of a vaccine has allowed C.
trachomatis to maintain its status as a significant public health threat. As an intracellular pathogen, C. trachomatis
is insulated from many host immune effectors. Additionally, downstream effects of IFN, a cytokine released by
host immune cells to combat infection, cause Chlamydia to transition into a persistent state – a viable yet non-
replicative and non-infectious state that specializes in survival rather than growth. In the absence of growth,
immune pressure dissipates, allowing C. trachomatis to revert back to its developmentally competent state and
continue the infection cycle. Considering Chlamydia’s asymptomatic nature and the difficulty in developing an
effective vaccine, a prophylactic drug treatment may be the best alternative – one specifically designed to inhibit
chlamydial persistence. Unfortunately, developing a prophylactic to target the persistent response is not currently
plausible since the molecular mechanisms involved in entering, maintaining, and exiting persistence are largely
unknown. Current knowledge is limited to broad observations in the persistent response, such as the
dysregulation of transcription and a decrease in translation. We hypothesize that a decrease in translation results
in the loss of transcriptional repressors, allowing sigma factors to become overactive in initiating transcription.
This proposal aims to characterize transcriptional changes associated with the initiation and maintenance of the
persistent state through combined RNA sequencing and chromatin immunoprecipitation and sequencing (ChIP
seq) approaches. IFN and two additional models shown to induce persistence will be used to observe
transcriptional changes associated with persistence via RNA seq. To gain further insight into the dynamics of
transcriptional changes, ChIP seq will be performed during persistence using multiple strains of C. trachomatis,
each harboring an endogenous polyhistidine tag on a different sigma factor. In addition to providing the first
genome wide analysis of sigma factor activity in C. trachomatis during standard growth and persistence,
transcriptional changes observed by RNA seq will be linked to specific sigma factors. This high resolution map
of transcriptional changes that occur during persistence will direct future investigations aimed at uncovering the
molecular mechanisms involved in the persistent response. Training under this fellowship will provide extensive
experience in state-of-the-art chlamydial molecular techniques, next generation sequencing, analysis of large
data sets, and scientific writing and presentation. Home to both a Genomics Core Facility and Bioinfor...

## Key facts

- **NIH application ID:** 10480774
- **Project number:** 5F31AI164863-02
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Nathan D. Hatch
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $35,525
- **Award type:** 5
- **Project period:** 2021-07-21 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10480774

## Citation

> US National Institutes of Health, RePORTER application 10480774, Defining the persistence associated transcriptome in Chlamydia trachomatis (5F31AI164863-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10480774. Licensed CC0.

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