# Genome-wide analysis of lateral gene transfer in Chlamydia trachomatis

> **NIH NIH R21** · OREGON STATE UNIVERSITY · 2020 · $238,375

## Abstract

The obligate intracellular bacteria chlamydiae cause serious diseases in both humans and
animals. Human infections by Chlamydia trachomatis number in the millions per year and lead to
serious pathologies in the eye and genital tract. Several unique characteristics define the genus
Chlamydia, one of which is the formation of large, polyploid, nonculturable persistent cell forms-
termed aberrant forms- that occur when the growing bacteria are exposed to stress. The biological
reasons that Chlamydia spp. have evolved this unusual growth form are completely unknown.
Genomic and laboratory-based studies demonstrate that clinical C. trachomatis undergoes a high
level of lateral gene transfer (LGT) within the species, but essentially no genetic exchange with
organisms outside the species. Any mechanism associated with chlamydial LGT remains
undiscovered, as does the biological reason for this process. This proposal will explore possible
interactions between the formation of aberrant forms and the process of lateral gene
transfer/recombination in the chlamydial system. Our overarching hypothesis is that that the
polyploid aberrant form facilitates intraspecies LGT and recombination, leading to recovery from
stress-induced mutagenesis during persistence inside cells. Intraspecies LGT can be modeled
very effectively in the laboratory using differently antibiotic resistant parents with modest levels of
genetic diversity. This proposal expands on that model, using in vitro conditions to mimic stresses
and selective forces that might be encountered in vivo. In Aim 1 we will use culture and genome
sequencing to explore the breadth and depth of LGT in cocultures of different C. trachomatis, and
evaluate qualitatively and quantitatively the effects of different stressors on the process. The
conditions to be tested include tryptophan starvation, beta-lactam exposure, and culture in the
presence of neutralizing antibodies. In Aim 2, we will use plasmid constructs to explore
recombination within individual C. trachomatis developmental forms, with constructs that carry
untranslatable resistance markers transformed into antibiotic-sensitive strains. We will examine
the phenotypic shift to antibiotic resistance within these strains, in the presence and absence of
stressors. This aim will test the hypothesis that recombination within individual developmental
forms is affected by the polyploidy introduced by a stress-induced transformation to aberrancy.
Collectively, these experiments will explore different aspects of how stress and aberrancy affect
the rate of lateral gene transfer and recombination in C. trachomatis. We will use these data to
examine the possible roles that chlamydial LGT and recombination serve in stress survival during
persistent infections of patients.

## Key facts

- **NIH application ID:** 10057794
- **Project number:** 1R21AI144865-01A1
- **Recipient organization:** OREGON STATE UNIVERSITY
- **Principal Investigator:** DANIEL D ROCKEY
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $238,375
- **Award type:** 1
- **Project period:** 2020-07-06 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10057794

## Citation

> US National Institutes of Health, RePORTER application 10057794, Genome-wide analysis of lateral gene transfer in Chlamydia trachomatis (1R21AI144865-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10057794. Licensed CC0.

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