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000288881 1001_ $$aRosendahl Huber, Axel$$b0
000288881 245__ $$aImproved detection of colibactin-induced mutations by genotoxic E. coli in organoids and colorectal cancer.
000288881 260__ $$aNew York, NY$$bElsevier$$c2024
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000288881 520__ $$aCo-culture of intestinal organoids with a colibactin-producing pks+E. coli strain (EcC) revealed mutational signatures also found in colorectal cancer (CRC). E. coli Nissle 1917 (EcN) remains a commonly used probiotic, despite harboring the pks operon and inducing double strand DNA breaks. We determine the mutagenicity of EcN and three CRC-derived pks+E. coli strains with an analytical framework based on sequence characteristic of colibactin-induced mutations. All strains, including EcN, display varying levels of mutagenic activity. Furthermore, a machine learning approach attributing individual mutations to colibactin reveals that patients with colibactin-induced mutations are diagnosed at a younger age and that colibactin can induce a specific APC mutation. These approaches allow the sensitive detection of colibactin-induced mutations in ∼12% of CRC genomes and even in whole exome sequencing data, representing a crucial step toward pinpointing the mutagenic activity of distinct pks+E. coli strains.
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000288881 650_7 $$2Other$$abacteria
000288881 650_7 $$2Other$$acancer genomics
000288881 650_7 $$2Other$$acolibactin
000288881 650_7 $$2Other$$acolorectal cancer
000288881 650_7 $$2Other$$agenotoxins
000288881 650_7 $$2Other$$amachine learning
000288881 650_7 $$2Other$$amutagenesis
000288881 650_7 $$2Other$$amutational signatures
000288881 650_7 $$2Other$$aorganoids
000288881 650_7 $$2Other$$aprobiotics
000288881 7001_ $$aPleguezuelos-Manzano, Cayetano$$b1
000288881 7001_ $$0P:(DE-He78)04965ffa43dd78e7f52259c5fceffefa$$aPuschhof, Jens$$b2$$udkfz
000288881 7001_ $$aUbels, Joske$$b3
000288881 7001_ $$aBoot, Charelle$$b4
000288881 7001_ $$0P:(DE-He78)daabfe66389621c1821e260f1793bb79$$aSaftien, Aurelia$$b5$$udkfz
000288881 7001_ $$aVerheul, Mark$$b6
000288881 7001_ $$aTrabut, Laurianne T$$b7
000288881 7001_ $$aGroenen, Niels$$b8
000288881 7001_ $$avan Roosmalen, Markus$$b9
000288881 7001_ $$0P:(DE-He78)bfd25fb9bbf13ba9c868ffc5fb634607$$aOuyang, Kyanna S$$b10$$udkfz
000288881 7001_ $$aWood, Henry$$b11
000288881 7001_ $$aQuirke, Phil$$b12
000288881 7001_ $$aMeijer, Gerrit$$b13
000288881 7001_ $$aCuppen, Edwin$$b14
000288881 7001_ $$aClevers, Hans$$b15
000288881 7001_ $$avan Boxtel, Ruben$$b16
000288881 773__ $$0PERI:(DE-600)2074034-7$$a10.1016/j.ccell.2024.02.009$$gVol. 42, no. 3, p. 487 - 496.e6$$n3$$p487 - 496.e6$$tCancer cell$$v42$$x1535-6108$$y2024
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