核梭杆菌
结直肠癌
氟尿嘧啶
癌症
癌症研究
体内
梭杆菌
化疗
微生物学
抗生素
西妥昔单抗
生物
医学
药理学
内科学
细菌
拟杆菌
遗传学
牙龈卟啉单胞菌
作者
Kaitlyn D LaCourse,Martha A. Zepeda-Rivera,Andrew G. Kempchinsky,Alexander Baryiames,Samuel S. Minot,Christopher A. Johnston,Susan Bullman
出处
期刊:Cell Reports
[Elsevier]
日期:2022-11-01
卷期号:41 (7): 111625-111625
被引量:30
标识
DOI:10.1016/j.celrep.2022.111625
摘要
Fusobacterium nucleatum (Fn) is a dominant bacterial species in colorectal cancer (CRC) tissue that is associated with cancer progression and poorer patient prognosis. Following a small-molecule inhibitor screen of 1,846 bioactive compounds against a Fn CRC isolate, we find that 15% of inhibitors are antineoplastic agents including fluoropyrimidines. Validation of these findings reveals that 5-fluorouracil (5-FU), a first-line CRC chemotherapeutic, is a potent inhibitor of Fn CRC isolates. We also identify members of the intratumoral microbiota, including Escherichia coli, that are resistant to 5-FU. Further, CRC E. coli isolates can modify 5-FU and relieve 5-FU toxicity toward otherwise-sensitive Fn and human CRC epithelial cells. Lastly, we demonstrate that ex vivo patient CRC tumor microbiota undergo community disruption after 5-FU exposure and have the potential to deplete 5-FU levels, reducing local drug efficacy. Together, these observations argue for further investigation into the role of the CRC intratumoral microbiota in patient response to chemotherapy.
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