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Published on: October 13, 2015
Chromatin accessibility and gene expression in the parasite Trichomonas vaginalis
Agustina Prat1, Daniela Muñoz1, Ayelen Lizarraga1
1Instituto Tecnológico Chascomús (INTECH), CONICET-UNSAM.
Abstract:
Trichomonas vaginalis, the most common non-viral sexually transmitted parasite, causes more than 270 million infections annually. The infection's outcome varies greatly depending on different factors that include variation in human immune responses, the vaginal microbiome, and the inherent virulence of the strain. Although the pathogenicity of the different strains depends, at least partially, on differential gene expression of virulence genes; the regulatory mechanisms governing this transcriptional control remain incompletely understood. While many studies have reported a positive correlation between gene expression and chromatin accessibility in other cells, this relationship has not been analyzed in T. vaginalis. To address these questions, we selected two contrasting T. vaginalis strains based on their interactions with host cells: B7268 strain, a highly adherent one and resistant to metronidazole, and NYH209 strain, a poorly adherent one and sensitive to metronidazole. Next, we combined the assay for transposase-accessible chromatin using sequencing (ATAC-seq) with RNA sequencing (RNA-seq), to delve into the relationship between chromatin accessibility and gene expression in these distinct T. vaginalis strains. Our findings demonstrate a correlation between chromatin accessibility and gene expression across both strains. Moreover, we found that chromatin accessibility plays a pivotal role in modulating mRNA expression levels of several established genes linked to parasite pathogenesis and drug resistance. We also identified several open chromatin peaks residing at intergenic regions, revealing possible distal regulatory elements that may control gene expression. These results highlight the importance of chromatin accessibility in modulating gene expression in the parasite T. vaginalis, with possible consequences in pathogenesis and/or drug treatment.
Insights
Chromatin accessibility influences gene expression in Trichomonas vaginalis, impacting parasite virulence and drug resistance. This study reveals key regulatory mechanisms in this common sexually transmitted infection.
Area of Science:
- Microbiology
- Genomics
- Parasitology
Background:
- Trichomonas vaginalis is a common sexually transmitted parasite responsible for millions of infections globally.
- Infection outcomes vary due to host immunity, microbiome, and parasite strain virulence, partly controlled by gene expression.
- Regulatory mechanisms of virulence gene expression in T. vaginalis remain poorly understood.
Purpose of the Study:
- To investigate the relationship between chromatin accessibility and gene expression in T. vaginalis.
- To compare these regulatory mechanisms between a highly adherent, metronidazole-resistant strain (B7268) and a poorly adherent, metronidazole-sensitive strain (NYH209).
Main Methods:
- Utilized Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) combined with RNA sequencing (RNA-seq).
- Analyzed two distinct T. vaginalis strains with contrasting adherence and drug resistance phenotypes.
Main Results:
- Demonstrated a significant correlation between chromatin accessibility and gene expression in both T. vaginalis strains.
- Identified chromatin accessibility as a key regulator of mRNA levels for genes associated with parasite pathogenesis and drug resistance.
- Discovered open chromatin regions in intergenic areas, suggesting potential distal regulatory elements.
Conclusions:
- Chromatin accessibility is crucial for modulating gene expression in T. vaginalis.
- These findings offer insights into parasite pathogenesis and potential therapeutic targets for drug resistance.
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