Bacterium rewrites gene regulation in host cells
A bacterium that causes pneumonia and sexually transmitted infections does something unexpected. It sabotages the way host cells regulate their genes, by disabling enzymes that normally remove DNA labels. The result is a fundamental disruption of cellular identity.
Chlamydia trachomatis is a common bacterium that infects cells from the inside. It steals nutrients from the host cell to fuel its own growth. But the study, published in eLife, shows that the damage goes further than nutrient theft. The bacterium also disrupts histones, the proteins around which DNA is wrapped and which determine which genes are active. Specifically, the histones become hypermethylated: they accumulate too many chemical labels (methyl groups) that normally regulate gene activity.
How the bacterium manipulates host cell chemistry
Histone methylation and its removal (demethylation) are balanced in a healthy cell. Chlamydia disrupts that balance through an indirect route. It consumes metabolic products of the host cell, causing succinate concentrations to rise in the cell nucleus. Succinate blocks the enzymes that remove methyl labels from histones. Those enzymes also require iron, the availability of which the bacterium reduces. When researchers supplemented cultured cells with additional co-factors, the hypermethylation decreased. This suggests the mechanism is active and reversible, at least in the laboratory.
Epigenetic changes, meaning alterations in gene regulation without changing the DNA sequence itself, are normally temporary and correctable. But chronic infections may break that reversibility. Whether the changes found in this study are fully restored after the bacterium is cleared is not evident from the data.
Relevant to aging and chronic infection
For the longevity field, this research raises a broader question: to what extent do past infections contribute to lasting changes in gene regulation? If bacteria can persistently disrupt the histone methylation of host cells, that may have long-term consequences for cellular aging and tissue health. That said, this is an interpretive step; the study itself investigated infection mechanisms in cell culture and a mouse model, not aging.
Search terms for further research: histone methylation infection epigenetics, succinate demethylase inhibition host cell, Chlamydia epigenetic modification chromatin