Kiguchi Yuya, Hamamoto Nagisa, Kashima Yukie, Runtuwene Lucky R, Ishizaka Aya, Kuze Yuta, Enokida Tomohiro, Tanaka Nobukazu, Tahara Makoto, Kageyama Shun-Ichiro, Fujisawa Takao, Yamashita Riu, Kanai Akinori, Tuda Josef S B, Mizutani Taketoshi, Suzuki Yutaka
Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Japan.
Laboratory for Symbiotic Microbiome Sciences, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Nat Commun. 2025 Aug 11;16(1):7397. doi: 10.1038/s41467-025-62406-5.
Survival strategy of bacteria is expanded by extrachromosomal elements (ECEs). However, their genetic diversity and functional roles for adaptability are largely unknown. Here, we discover a novel family of intracellular ECEs using 56 saliva samples by developing an efficient microbial DNA extraction method coupled with long-read metagenomics assembly. Even though this ECE family was not hitherto identified, our global prevalence analysis using 476 salivary metagenomic datasets elucidates that these ECEs reside in 74% of the population. These ECEs, which we named, "Inocles", are giant plasmid-like circular genomic elements of 395 kb in length, including Streptococcus as a host bacterium. Inocles encode a series of genes that contribute to intracellular stress tolerance, such as oxidative stress and DNA damage, and cell wall biosynthesis and modification involved in the interactions with oral epithelial cells. Moreover, Inocles exhibit significant positive correlations with immune cells and proteins responding to microbial infection in peripheral blood. Intriguingly, we examine and find their marked reductions among 68 patients of head and neck cancers and colorectal cancers, suggesting its potential usage for a novel biomarker of gastrointestinal cancers. Our results suggest that Inocles potentially boost the adaptive capacity of host bacteria against various stressors in the oral environment.
细菌的生存策略通过染色体外元件（ECEs）得以扩展。然而，它们的遗传多样性及其在适应性方面的功能作用在很大程度上尚不清楚。在此，我们通过开发一种高效的微生物DNA提取方法并结合长读长宏基因组组装，利用56份唾液样本发现了一个新的细胞内ECEs家族。尽管此前尚未鉴定出这个ECEs家族，但我们使用476个唾液宏基因组数据集进行的全球流行率分析表明，这些ECEs存在于74%的人群中。我们将这些ECEs命名为“Inocles”，它们是长度为395 kb的巨大质粒样环状基因组元件，宿主细菌为链球菌。Inocles编码一系列有助于细胞内应激耐受的基因，如氧化应激和DNA损伤，以及参与与口腔上皮细胞相互作用的细胞壁生物合成和修饰。此外，Inocles与外周血中对微生物感染作出反应的免疫细胞和蛋白质呈现出显著的正相关。有趣的是，我们检查发现，在68例头颈癌和结直肠癌患者中它们显著减少，这表明其在作为胃肠道癌症新型生物标志物方面具有潜在用途。我们的结果表明，Inocles可能增强宿主细菌在口腔环境中抵抗各种应激源的适应能力。
