Metabolic imprint of an intracellular pathogen drives histone hypermethylation and tunes the host transcriptional response to infection

ABSTRACT: Chlamydia trachomatis, an obligate intracellular bacterium, highjacks metabolites from the host cell to sustain its own growth. We provide evidence of global hypermethylation of the host proteome, including histones, during the late stages of infection and that histone hypermethylation is the result of metabolic imbalance favoring the activity of lysine methyl transferases over demethylases. Hypermethylation at residues histone H3 lysine 4 (H3K4) and H3K9 spread throughout the chromatin. Inhibition of bacterial growth, or supplementation of the culture medium with iron or with dimethyl-ketoglutarate (DMKG) reduced histone hypermethylation. DMKG supplementation modified the transcriptional response to infection of about one third of the infection-responsive genes, including genes involved in the innate response to infection. Transfer RNA (tRNA) levels decreased late in infection and DMKG supplementation prevented this phenomenon. Finally, we uncovered a robust, histone demethylase dependent shut-down of the innate response to infection in the mouse genital tract shortly after the acute phase of infection. Overall, our data demonstrate that the host transcriptomic response to infection integrates the metabolic pressure exerted by the proliferating pathogen.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human) Chlamydia Trachomatis Serovar L2 (strain 434/bu / Atcc Vr-902b)

SUBMITTER: Magalie Duchateau  

LAB HEAD: Agathe Subtil

PROVIDER: PXD051857 | Pride | 2026-10-05

REPOSITORIES: Pride