Jacobs Jodie, Mirchandani Cade, Seligmann William E, Sacco Samuel, Escalona Merly, Green Richard E, Russell Shelbi L
Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA, United States. Genomics Institute, University of California Santa Cruz, Santa Cruz, CA 95064.
bioRxiv. 2025 Jun 6:2025.06.05.658111. doi: 10.1101/2025.06.05.658111.
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.
许多与宿主相关的细菌会影响其真核宿主细胞的分化。[具体细菌名称1]和[具体细菌名称2]之间的关联为理解宿主-微生物基因表达如何共同进化提供了一个模型。利用感染了[具体细菌名称1]的[具体细胞系名称]细胞系，我们发现Mel菌株会改变宿主细胞状态，诱导出与已知细胞类型不同的新基因表达程序。转录组共表达网络分析确定了每种细胞类型和感染状态特有的基因表达模块，并揭示Mel会根据宿主环境调整其基因表达。在巨噬细胞样宿主细胞中，Mel表达致病效应子，而在神经元样细胞中，Mel上调代谢基因。Micro-C染色质接触数据表明，许多这些感染诱导的变化是由表观遗传编码的，Mel感染导致[具体细胞系名称]中染色质接触减少和广泛的转录去抑制。这些发现表明，[具体细菌名称1]共生的性质——互利共生或致病——取决于宿主细胞环境，并为设计宿主特异性微生物表型提出了新途径。
