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Updated: Aug 29, 2026
Live-Cell Forward Genetic Approach to Identify and Isolate Developmental Mutants in Chlamydia trachomatis
Published on: June 10, 2020
Transcriptome analysis of chlamydial growth during IFN-gamma-mediated persistence and reactivation
Robert J Belland1, David E Nelson, Dezso Virok
1Laboratories of Intracellular Parasites and Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
Abstract:
Chlamydia trachomatis is an obligatory intracellular prokaryotic parasite that causes a spectrum of clinically important chronic inflammatory diseases of humans. Persistent infection may play a role in the pathophysiology of chlamydial disease. Here we describe the chlamydial transcriptome in an in vitro model of IFN-gamma-mediated persistence and reactivation from persistence. Tryptophan utilization, DNA repair and recombination, phospholipid utilization, protein translation, and general stress genes were up-regulated during persistence. Down-regulated genes included chlamydial late genes and genes involved in proteolysis, peptide transport, and cell division. Persistence was characterized by altered but active biosynthetic processes and continued replication of the chromosome. On removal of IFN-gamma, chlamydiae rapidly reentered the normal developmental cycle and reversed transcriptional changes associated with cytokine treatment. The coordinated transcriptional response to IFN-gamma implies that a chlamydial response stimulon has evolved to control the transition between acute and persistent growth of the pathogen. In contrast to the paradigm of persistence as a general stress response, our findings suggest that persistence is an alternative life cycle used by chlamydiae to avoid the host immune response.
Insights
Chlamydia trachomatis uses a unique life cycle to persist during host immune responses. Reactivation occurs rapidly upon removal of interferon-gamma (IFN-γ), indicating a controlled survival strategy.
Area of Science:
- Microbiology
- Infectious Diseases
- Molecular Biology
Background:
- Chlamydia trachomatis is an intracellular bacterium causing chronic inflammatory diseases.
- Persistent infection is implicated in chlamydial disease pathophysiology.
- Understanding chlamydial persistence mechanisms is crucial for disease control.
Purpose of the Study:
- To investigate the chlamydial transcriptome during interferon-gamma (IFN-γ)-mediated persistence and reactivation.
- To elucidate the molecular mechanisms underlying chlamydial persistence and survival.
Main Methods:
- In vitro culture model of Chlamydia trachomatis infection.
- Transcriptome analysis using RNA sequencing.
- Interferon-gamma (IFN-γ) treatment and withdrawal to induce and reverse persistence.
Main Results:
- Persistence involved up-regulation of tryptophan utilization, DNA repair, phospholipid utilization, protein translation, and stress genes.
- Down-regulated genes included late genes, proteolysis, peptide transport, and cell division genes.
- Chlamydiae reactivated rapidly upon IFN-γ removal, reversing transcriptional changes.
Conclusions:
- Chlamydia trachomatis exhibits a coordinated transcriptional response to IFN-γ, suggesting an evolved "response stimulon".
- Persistence represents an alternative life cycle, not merely a general stress response.
- This alternative life cycle aids Chlamydia trachomatis in evading host immune responses.
