Multi-omics analyses of cancer-linked clinical salmonellae reveal bacterial-induced host metabolic shift and mTOR-dependent cell transformation.

IF 7.5 1区 生物学 Q1 CELL BIOLOGY Cell reports Pub Date : 2024-11-01 DOI:10.1016/j.celrep.2024.114931
Virginie Stévenin, Claudia E Coipan, Janneke W Duijster, Daphne M van Elsland, Linda Voogd, Lise Bigey, Angela H A M van Hoek, Lucas M Wijnands, Lennert Janssen, Jimmy J L L Akkermans, Andra Neefjes-Borst, Eelco Franz, Lapo Mughini-Gras, Jacques Neefjes
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Abstract

Salmonellae are associated epidemiologically and experimentally with colon cancer. To understand how Salmonella induces cell transformation, we performed multi-omics and phenotypic analyses of Salmonella clinical strains isolated from patients later diagnosed with colon cancer (case strains) and control strains from patients without cancer. We show that high transformation efficiency is a frequent intrinsic feature of clinical (case and control) salmonellae, yet case strains showed higher transformation efficiency than control strains. Transformation efficiency correlates with gene expression, nutrient utilization, and intracellular virulence, but not with genetic features, suggesting a phenotypic convergence of Salmonella strains resulting in cell transformation. We show that both bacterial entry and intracellular replication are required for host cell transformation and are associated with hyperactivation of the mTOR pathway. Strikingly, transiently inactivating mTOR through chemical inhibition reverses the transformation phenotype instigated by Salmonella infection. This suggests that targeting the mTOR pathway could prevent the development of Salmonella-induced tumors.

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癌症相关临床沙门氏菌的多组学分析揭示了细菌诱导的宿主代谢转变和依赖 mTOR 的细胞转化。
沙门氏菌在流行病学和实验上与结肠癌有关。为了了解沙门氏菌是如何诱导细胞转化的,我们对从后来确诊为结肠癌的患者(病例菌株)中分离出的临床沙门氏菌菌株和从未患过癌症的患者中分离出的对照菌株进行了多组学和表型分析。我们发现,高转化效率是临床(病例和对照)沙门氏菌的一个常见固有特征,但病例菌株的转化效率高于对照菌株。转化效率与基因表达、营养利用和细胞内毒力相关,但与遗传特征无关,这表明沙门氏菌菌株的表型趋同导致了细胞转化。我们的研究表明,宿主细胞转化需要细菌进入和细胞内复制,并且与 mTOR 通路的过度激活有关。令人震惊的是,通过化学抑制剂使 mTOR 暂时失活可逆转沙门氏菌感染引发的转化表型。这表明,靶向 mTOR 通路可以防止沙门氏菌诱发肿瘤的发生。
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来源期刊
Cell reports
Cell reports CELL BIOLOGY-
CiteScore
13.80
自引率
1.10%
发文量
1305
审稿时长
77 days
期刊介绍: Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.
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