induces host cell identity changes and determines symbiotic fate in .

Many host-associated bacteria influence the differentiation of their eukaryotic host cells. The association between and offers a model for understanding how host-microbe gene expression co-evolves. Using -infected cell lines, we show that the Mel strain alters host cell states, inducing novel gene expression programs that diverge from known cell types. Transcriptomic co-expression network analysis identified gene expression modules specific to each cell type and infection state, and revealed that Mel tailors its gene expression to host context. In macrophage-like host cells, Mel expresses pathogenic effectors, whereas in neuron-like cells, Mel upregulates metabolic genes. Micro-C chromatin contact data revealed that many of these infection-induced changes are epigenetically encoded, with Mel infection conferring reduced chromatin contacts and widespread transcriptional derepression in . These findings show that the nature of symbiosis-mutualistic or pathogenic-emerges from host cell environments and suggest new paths for engineering host-specific microbial phenotypes.