Colibactin 主要由 B2 系统群的大肠杆菌菌株产生，可交联 DNA，并可促进人类宿主罹患结肠癌。我们研究了该毒素对大肠杆菌素生产者以及与生产细胞共培养的细菌的影响。通过全基因组遗传筛选和突变积累实验，我们发现了减轻大肠杆菌素损伤的细胞途径，并揭示了它诱导的特定突变。我们发现，虽然大肠杆菌素靶向富含 A/T 的基序，如在人类结肠细胞中观察到的那样，但它会诱导细菌独特的突变模式。基于这种模式，我们预测长期接触大肠杆菌素将最终导致三核苷酸组成的基因组偏差。我们通过分析数千个大肠杆菌基因组来测试这一预测，发现产生大肠杆菌素的菌株确实在三核苷酸组成中表现出预测的偏度。我们的工作揭示了细菌特异性突变模式，并表明大肠杆菌素致病岛上编码的抗性蛋白不足以防止自身造成的 DNA 损伤。由冷泉港实验室出版社出版。

Colibactin produced primarily by Escherichia coli strains of the B2 phylogroup crosslinks DNA and can promote colon cancer in human hosts. We investigated the toxin's impact on colibactin producers and on bacteria co-cultured with producing cells. Using genome-wide genetic screens and mutation accumulation experiments we uncovered the cellular pathways that mitigate colibactin damage and revealed the specific mutations it induces. We discovered that while colibactin targets A/T rich motifs, as observed in human colon cells, it induces a bacteria-unique mutation pattern. Based on this pattern, we predicted that long-term colibactin exposure will culminate in a genomic bias in trinucleotide composition. We tested this prediction by analyzing thousands of E. coli genomes and found that colibactin-producing strains indeed show the predicted skewness in trinucleotide composition. Our work revealed a bacteria-specific mutation pattern and suggests that the resistance protein encoded on the colibactin pathogenicity island is insufficient in preventing self-inflicted DNA damage.Published by Cold Spring Harbor Laboratory Press.