Lee Jae Min, Yang Hyun Oh, Tanizawa Hideki, Noma Ken-Ichi, Lee Tae Kwon, Jung Won Hee, Cho Yong-Joon, Kim Kyoung-Dong
Department of Systems Biotechnology, Chung-ang University, Anseong, Republic of Korea.
Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
mBio. 2025 Sep 12:e0159225. doi: 10.1128/mbio.01592-25.
The skin microbiome is composed of diverse microbial communities that engage in interkingdom interactions, influencing host physiology and microbial balance. Although and are codominant members of the human skin microbiome, the molecular mechanisms underlying their interactions remain poorly understood. We aimed to investigate the mechanism by which -derived acetic acid affects chromatin organization and gene expression in modulated chromatin structure and transcriptional activity in by secreting acetic acid (AcOH), a common skin-associated organic acid. Using Hi-C, we established the first three-dimensional genome architecture map of and identified putative centromeric loci based on inter-chromosomal association scores. Co-culture with or direct treatment with AcOH induced large-scale chromatin decompaction and enhanced centromeric clustering, indicating significant reorganization of the nuclear architecture. Through chromatin immunoprecipitation (ChIP)-seq analysis, we observed that AcOH exposure led to a redistribution of histone acetylation from promoter regions to gene bodies. This chromatin remodeling was further associated with extensive transcriptional repression, particularly of genes involved in translation, metabolism, and virulence, as revealed by RNA-seq analysis. Of note, these changes were specific to AcOH and were not replicated under inorganic acid stress (HCl), indicating a metabolite-specific epigenetic response. This study reveals a novel form of interkingdom communication in the skin microbiome, in which -derived AcOH acts as an epigenetic modulator in . Our findings provide key mechanistic insights into how bacterial metabolites influence fungal chromatin architecture and transcription, with implications for microbial community dynamics and skin health.IMPORTANCEThis study provides essential insights into interkingdom interactions within the human skin microbiome, highlighting how microbial metabolites influence fungal biology at the chromatin level. Specifically, we identify acetic acid (AcOH), secreted by , as a key regulator that induces significant chromatin remodeling and transcriptional changes in . By presenting the first three-dimensional genome architecture map of , our findings uncover metabolite-specific chromatin dynamics that cannot be replicated by inorganic acid stress. Additionally, the conservation of this chromatin response in other species suggests broader implications for understanding microbial adaptation mechanisms in the skin environment. This work underscores the critical role of bacterial metabolites as modulators of microbial interactions and provides new avenues for investigating microbial community balance and potential therapeutic strategies for skin health.
皮肤微生物群由多种微生物群落组成，这些群落参与跨界相互作用，影响宿主生理和微生物平衡。尽管[具体微生物名称1]和[具体微生物名称2]是人类皮肤微生物群的共优势成员，但其相互作用的分子机制仍知之甚少。我们旨在研究[具体微生物名称1]产生的乙酸如何影响[具体微生物名称2]中的染色质组织和基因表达，[具体微生物名称1]通过分泌乙酸（AcOH，一种常见的与皮肤相关的有机酸）来调节[具体微生物名称2]中的染色质结构和转录活性。使用[具体技术名称]Hi-C，我们建立了[具体微生物名称2]的首个三维基因组结构图，并根据染色体间关联分数确定了假定的着丝粒位点。与[具体微生物名称1]共培养或用AcOH直接处理会诱导大规模染色质解压缩并增强着丝粒聚集，表明核结构发生了显著重组。通过染色质免疫沉淀（ChIP）-seq分析，我们观察到暴露于AcOH会导致组蛋白乙酰化从启动子区域重新分布到基因体。这种染色质重塑进一步与广泛的转录抑制相关，特别是与参与翻译、代谢和毒力的基因相关，RNA-seq分析揭示了这一点。值得注意的是，这些变化是AcOH特有的，在无机酸胁迫（HCl）下不会重现，表明这是一种代谢物特异性的表观遗传反应。这项研究揭示了皮肤微生物群中一种新的跨界通讯形式，其中[具体微生物名称1]产生的AcOH在[具体微生物名称2]中作为表观遗传调节剂起作用。我们的研究结果为细菌代谢物如何影响真菌染色质结构和转录提供了关键的机制见解，对微生物群落动态和皮肤健康具有重要意义。
重要性
本研究为人类皮肤微生物群中的跨界相互作用提供了重要见解，突出了微生物代谢物在染色质水平上如何影响真菌生物学。具体而言，我们确定[具体微生物名称1]分泌的乙酸（AcOH）是诱导[具体微生物名称2]中显著染色质重塑和转录变化的关键调节因子。通过展示[具体微生物名称2]的首个三维基因组结构图，我们的研究结果揭示了无机酸胁迫无法重现的代谢物特异性染色质动态。此外，这种染色质反应在其他[具体微生物名称2]物种中的保守性表明，对于理解皮肤环境中的微生物适应机制具有更广泛的意义。这项工作强调了细菌代谢物作为微生物相互作用调节剂的关键作用，并为研究微生物群落平衡和皮肤健康的潜在治疗策略提供了新途径。
