#FEMSmicroBlog: Pathogenic Chlamydia triggering epigenetic changes


The species Chlamydia trachomatis, Chlamydia pneumoniae, and Chlamydia psittaci are linked to human diseases and can create medical and public health burdens. As part of their survival strategies, all three Chlamydia species modulate epigenetic changes within the infected host cell promoting pathogenesis. The minireview “Epigenetic changes induced by pathogenic Chlamydia spp” in Pathogens and Disease discusses the epigenetic mechanisms that this intracellular bacterium applies as its key virulence mechanisms, as explained by Lily Thompson and Richard Stein. #FascinatingMicrobes


The three intracellular Chlamydia pathogens

These three obligate intracellular Chlamydia species are of high concern for public health organizations:

Firstly, Chlamydia trachomatis infects the ocular and genital epithelia, which in 85-90% of cases are asymptomatic.

Secondly, Chlamydia pneumoniae is linked to asymptomatic or mild respiratory infections and medical conditions, such as asthma, arthritis, and lung cancer, but also to severe disease and even death. It is the most commonly implicated infectious agent in the pathogenesis of atherosclerotic cardiovascular disease and is involved in neurodegenerative conditions, such as Alzheimer’s disease.

Thirdly, Chlamydia psittaci is primarily an avian pathogen. Yet, it can cause flu-like diseases in humans and community-acquired pneumonia.


Epigenetic changes controlling Chlamydia pathogenesis

For pathogenesis, Chlamydia employs several efficient and specific epigenetic changes, which numerous recent studies focused on. The three main types of epigenetic changes are DNA methylation, histone post-translational modifications, and RNA interference. Notably, Chlamydia makes use of all of them during the infection process, as discussed in the minireview “Epigenetic changes induced by pathogenic Chlamydia spp” in Pathogens and Disease.

For example, Chlamydia-infected cells show promoter hypermethylation of the gene that encodes E-cadherin, thus downregulating its expression. On the contrary, the promoters of the genes encoding fibronectin and a-smooth muscle actin are modified by hypomethylation, leading to upregulation of gene expression.

While not yet completely understood, Chlamydia further controls the degradation and stability of a large number of microRNAs via RNA interference. Since a big part of the cellular microRNAome becomes dysregulated, this mechanism might impact tumorigenesis.

Lastly, Chlamydia species regulate chromatin accessibility through post-translational modifications of histones H3 and H4. These mechanisms seem to shape molecular processes during Chlamydia’s unique developmental cycle.


Chlamydia’s epigenetic changes trigger various diseases

Chlamydia’s ability to induce epigenetic changes is of considerable interest, as some of these changes may even trigger the transition of polarized epithelial to motile mesenchymal cells. This epithelial-to-mesenchymal-transition is extremely dynamic and potentially reversible.

During the epithelial-to-mesenchymal-transition, Chlamydia triggers the downregulation of adhesion molecules on epithelial cells, such as E-cadherin. At the same time, it promotes the upregulation of mesenchymal proteins, such as a-smooth muscle actin.

Over time, cells lose their epithelial properties and connective networks and acquire mesenchymal characteristics by becoming motile and acquiring invasive capabilities. This transition was described in both ocular and genital epithelia and might represent a mechanistic link between chronic inflammation, cancer, and fibrosis.

Endothelial-to-mesenchymal transition (EMT) triggered by Chlamydia.
Endothelial-to-mesenchymal transition (EMT) triggered by Chlamydia. From Stein and Thompson (2023).


The review further discusses additional epigenetic mechanisms that impact pathologies caused by Chlamydia. For example, this pathogen can inhibit apoptosis in the host cell by interfering with DNA repair mechanisms. Similarly, by suppressing cholesterol efflux from infected macrophages, it impacts the host’s lipid metabolism. As also shown in other pathogens, these disruptive mechanisms are linked to various diseases, such as cardiovascular disease.


Epigenetic changes hold great promises for the clinic

A unifying theme behind the epigenetic changes that contribute to the various pathologies is the possibility of recognizing them early, monitoring their progression over time, and reversing them with therapeutic interventions. One current obstacle is the insufficient understanding of how relevant epigenetic changes are for cells, cell lines, organoids, and animal models. An additional challenge is that the functions of many dysregulated miRNAs are not known, even more complicated by the fact that a single miRNA may regulate up to several hundreds of mRNAs.

Currently, no biomarkers exist to predict complications caused by Chlamydia. While still substantial research gaps exist, epigenetic changes may help identify and characterize signatures as diagnostic, prognostic, or therapeutic biomarkers.


About the authors of this blog

Lily M. Thompson is a fourth-year student at New York University studying Biomolecular Science with a minor in Public Health. She is interested in virology, infectious diseases, and gene therapy. Lily was involved in a US Department of Energy research project where she focused on developing and testing CRISPR interference systems in bacteria. She has also been involved in epidemiological research focusing on the impacts of COVID-19 on marginalized populations in New York City, presenting her findings at the American Public Health Association National Conference in 2022. Currently, Lily is researching genetic therapies for kidney disease, and exploring her other interests through her continued education.

Richard A. Stein is an Industry Associate Professor at NYU Tandon School of Engineering. He holds an MD from the “Iuliu Haţieganu” University of Medicine and Pharmacy, Romania, and a PhD in Biochemistry from the University of Alabama at Birmingham. Richard is interested in understanding the spread of infectious diseases in populations, with a particular focus on the phenomenon of super-spreading, and the way commensal and pathogenic microorganisms shape gene expression in the host by epigenetic mechanisms. Additionally, in recent years, Richard’s work has explored the impact that misinformation and disinformation, especially in the realm of science and health, may exert on public health. Richard likes traveling, volunteering at animal shelters, and climbing volcanoes.

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The section #FascinatingMicrobes for the #FEMSmicroBlog explains the science behind a paper and highlights the significance and broader context of a recent finding. One of the main goals is to share the fascinating spectrum of microbes across all fields of microbiology.

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