宿主细胞中的蛋白质后翻译修饰（PTM）可以被细菌酶重新编写，代表了肠道菌群与宿主之间通信的前所未有机制。虽然Akkermansia muciniphila被广泛调查作为一种益生菌，并能减弱小鼠结肠炎相关的肿瘤发生，但是对于A. muciniphila是否参与结直肠癌（CRC）的PTM，人们还知之甚少。本研究研究了A. muciniphila是否以及如何参与宿主CRC的PTM。使用A. muciniphila分泌的胞外囊泡和纯化的Amuc_2172研究了不同的肿瘤发生小鼠模型。在体内外评估了Amuc_2172诱导的CD8+细胞毒性T淋巴细胞（CTLs）的免疫活性。研究了Amuc_2172的乙酰转移酶活性和下游靶基因。Amuc_2172是A. muciniphila的一种通用控制非抑制性5相关乙酰转移酶，通过大胞吞噬作用易于进入结肠细胞，并在组蛋白H3（H3K14ac）的Lys14位点上发挥乙酰转移酶的作用。Hspa1a位点上升高的H3K14ac促进了癌细胞热休克蛋白70（HSP70）的转录和分泌。高水平的HSP70在体内外促进CTLs的免疫活性。此外，生物工程纳米颗粒为Amuc_2172提供了一种安全可靠的CRC治疗药物递送策略。Amuc_2172通过诱导HSP70分泌和促进CTL相关的免疫反应重编程了肿瘤微环境。 ©作者（或其雇主）2023。不得商业再利用。查看权利和权限。BMJ出版。

The protein post-translational modification (PTM) in host cells can be rewritten by bacterial enzymes and represents an unprecedented mechanism in the communication between intestinal flora and the host. Although Akkermansia muciniphila has been widely investigated as a probiotic and blunts colitis-associated tumourigenesis in mice, there is little understanding regarding whether A. muciniphila is involved in the PTM of colorectal cancer (CRC). This study investigates whether and how A. muciniphila engages in the PTM of host CRC.The secreting extracellular vesicles from A. muciniphila and purified Amuc_2172 were used for different tumourigenesis mice models. Amuc_2172-induced immune activity of CD8+ cytotoxic T lymphocytes (CTLs) were evaluated in vitro and in vivo. The acetyltransferase activity and downstream target genes of Amuc_2172 were investigated.Amuc_2172, a general control non-derepressible 5-related acetyltransferase of A. muciniphila, was accessible to colorectal cells by macropinocytosis and functioned as an acetyltransferase of Lys14 on histone H3 (H3K14ac). Elevated H3K14ac on Hspa1a loci promoted the transcription and secretion of heat-shock protein 70 (HSP70) in cancer cells. High level of HSP70 promoted the immune activity of CTLs in vitro and in vivo. Moreover, bioengineered nanoparticles provided a safe and reliable drug delivery strategy of Amuc_2172 for CRC treatment in an allograft mice model.Amuc_2172 reprogrammed tumour microenvironment by inducing HSP70 secretion and promoting CTL-related immune response in the process of tumourigenesis.© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.