Department of Biology, Division of Microbiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Staudtstr. 5, 91058 Erlangen, Germany.
Division of Bioinformatics, Institute of Biochemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg; 91054 Erlangen, Germany.
Trends Microbiol. 2024 Sep;32(9):847-857. doi: 10.1016/j.tim.2024.02.001. Epub 2024 Mar 13.
Several single-nucleotide polymorphisms (SNPs) in human chromosomes are known to predispose to cancer. However, cancer-associated SNPs in bacterial pathogens were unknown until discovered in the stomach pathogen Helicobacter pylori. Those include an alanine-threonine polymorphism in the EPIYA-B phosphorylation motif of the injected effector protein CagA that affects cancer risk by modifying inflammatory responses and loss of host cell polarity. A serine-to-leucine change in serine protease HtrA is associated with boosted proteolytic cleavage of epithelial junction proteins and introduction of DNA double-strand breaks (DSBs) in host chromosomes, which co-operatively elicit malignant alterations. In addition, H. pylori genome-wide association studies (GWAS) identified several other SNPs potentially associated with increased gastric cancer (GC) risk. Here we discuss the clinical importance, evolutionary origin, and functional advantage of the H. pylori SNPs. These exciting new data highlight cancer-associated SNPs in bacteria, which should be explored in more detail in future studies.
已知人类染色体上的几个单核苷酸多态性（SNP）容易导致癌症。然而，直到在胃部病原体幽门螺杆菌中发现之前，人们还不知道与细菌病原体相关的 SNP。其中包括注入效应蛋白 CagA 的 EPIYA-B 磷酸化模体中的丙氨酸-苏氨酸多态性，该多态性通过改变炎症反应和宿主细胞极性来影响癌症风险。丝氨酸蛋白酶 HtrA 中的丝氨酸到亮氨酸的变化与上皮连接蛋白的蛋白水解切割增强以及宿主染色体中的 DNA 双链断裂（DSB）有关，这两者共同引起恶性改变。此外，幽门螺杆菌全基因组关联研究（GWAS）还鉴定了其他几个可能与胃癌（GC）风险增加相关的 SNP。在这里，我们讨论了这些 SNP 的临床重要性、进化起源和功能优势。这些令人兴奋的新数据突出了细菌中与癌症相关的 SNP，未来的研究应更详细地探讨这些 SNP。
