Blanchet, L. | bioRxiv Science

bioRxiv2024

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

Chlamydia trachomatis, an intracellular bacterium, highjacks metabolites from the host cell for its own proliferation. We provide evidence of global hypermethylation of the host proteome, including histones, during the late stages of infection. Single cell analyses revealed co-occurrence of several methylated residues on histones. Histone hypermethylation correlated with bacterial load and was prevented by antibiotic treatment. Mapping of trimethylation of histone 3 at residues K4 and K9 revealed a broad distribution throughout the chromatin. Nuclear fractions of infected cells exhibited a four-fold decrease of demethylase activity towards H3K4me3 and a two-fold increase in succinate concentration, a competitive inhibitor for the demethylase co-factor -ketoglutarate. Supplementation of the culture medium with dimethyl-ketoglutarate (DMKG) or with iron, a second co-factor of histone lysine demethylases, reduced histone hypermethylation. DMKG supplementation modified the transcription of about one third of the infection-responsive genes, indicating that histone hypermethylation contributes to modulating the transcriptional response of the host to infection. Finally, chemical inhibition of histone demethylases in a mouse model of infection showed a moderate benefit regarding the outcome of infection. Overall, our data show that the metabolic pressure exerted by a pathogen with an intracellular lifestyle drives epigenetic changes in infected cells.

cell biology↗

bioRxiv2018

Effect of diapause on cold-resistance in different life-stages of an aphid parasitoid wasp

To overwinter, insects from mild temperate areas can either enter diapause or remain active. Both strategies involve costs and benefits depending on the environment. In the first case, the emerging individuals will resist winter but have a reduced fitness because diapause entails physiological and ecological costs. In the second case, individuals need to be cold-resistant enough to withstand winter temperatures during their immature and adult stages, but could avoid diapause-associated costs. In mild temperate areas, the cost-benefit balance between the diapause and the non-diapause strategy would likely change in response to climate warming. A trade-off between these two strategies should lead to reduction of diapause expression in some populations. We explored the importance of such trade-off through the comparison of cold resistance capacities among different life stages in diapause and non-diapause individuals in a population of the aphid parasitoid Aphidius ervi (Hymenoptera: Braconidae) originating from western France where a decrease of diapause incidence was recently observed. As a proxy measure of insect physiological cold resistance, the Super Cooling Point (SCP) was determined for non-diapausing and diapausing prepupae and adults that went through prepupal diapause or not. Diapausing and non-diapausing prepupae were equally cold-resistant (-24.20 {+/-}0.30{degrees}C vs. -24.74 {+/-}0.36{degrees}C, respectively), and overall more resistant than adults. Adults that went through diapause as prepupae were less cold resistant (-17.85 {+/-}1.10{degrees}C) than adults that have not undergone through diapause (-21.10 {+/-}0.54{degrees}C). We also found that diapausing prepupae and adults that have undergone diapause were lighter than their non-diapausing counterparts, at a comparable size, suggesting higher energetic expenses during diapause. These results suggest a trade-off between diapause expression in prepupae and cold resistance and life-history-traits in adults. We conclude that selection could favor insects that do not enter diapause and thus avoid its associated costs while taking advantage at exploiting the mild winter environment.

ecology↗