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The activation and functional differentiation of CD8 + T cells are linked to metabolic pathways that result in the production of lactate. Lactylation is a lactate-derived histone post-translational modification; however, the relevance of histone lactylation in the context of CD8 + T cell activation and function is not known. Here, we show the enrichment of H3K18 lactylation (H3K18la) and H3K9 lactylation (H3K9la) in human and mouse CD8 + T cells, which act as transcription initiators of key genes regulating CD8 + T cell function. Further, we note distinct patterns of H3K18la and H3K9la in CD8 + T cell subsets linked to their specific metabolic profiles. Additionally, we find that modulation of H3K18la and H3K9la by targeting metabolic and epigenetic pathways influence CD8 + T cell effector function, including antitumor immunity, in preclinical models. Overall, our study uncovers the potential roles of H3K18la and H3K9la in CD8 + T cells. Goswami and colleagues describe how lactylation of histone lysine residues regulates the transcriptome, metabolism and function of CD8 + T cells.

Enterococcus faecalis is an opportunistic pathogen involved in causing various hospital-acquired infections. Their propensity to develop antibiotic resistance by horizontal gene transfer via conjugative mobile genetic elements makes the treatment of E. faecalis infection increasingly difficult. Pheromone-responsive plasmids are involved in the transfer of mobile genetic elements in E. faecalis. CRISPR-Cas acts as a barrier against foreign genome transfer in bacteria. E. faecalis CRISPR-Cas activity varies in vivo (murine intestinal model) and in vitro. The functional differences may be due to various biotic and abiotic factors such as nutrient availability, community diversity, donor-to-recipient ratios, and cas9 regulatory differences. A previous study has shown that the efficacy of CRISPR-Cas varies in the presence of a microbial community. Here we study the effect of Escherichia coli, also a resident of the mammalian gut, on CRISPR-Cas defense in vitro using E. faecalis containing pAM714 plasmid. Through our work, we are able to demonstrate that CRISPR-Cas efficacy is not altered by the presence of E. coli during conjugation between donor OG1SSp (pAM714) and recipients T11RF and T11RFΔcas9. Our goal is to provide insights into CRISPR-Cas function of Gram-positive bacteria in the microbial community.