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Journal articles on the topic 'Colibactin'

Author: Grafiati

Published: 4 June 2021

Last updated: 18 May 2024

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1

Dougherty, Michael W., Rafael Valdés-Mas, Kevin M. Wernke, et al. "Abstract 1215: Synthetic colibactins reveal the structural and biological mode-of-action of a microbial carcinogen." Cancer Research 83, no. 7_Supplement (2023): 1215. http://dx.doi.org/10.1158/1538-7445.am2023-1215.

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Abstract Certain Enterobacteriaceae strains contain a 54-kb biosynthetic gene cluster referred to as “pks” encoding the biosynthesis of a secondary metabolite, colibactin, that putatively alkylates host DNA via nucleophilic cyclopropane ring addition. While evidence suggests colibactin’s genotoxicity promotes mutagenesis and cancer, it has been impossible to directly test this hypothesis due to compound instability and sparse production. Recently synthesized stable colibactin analogs facilitate the first studies investigating the compounds structural mode of action. We tested the genotoxic cap

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2

Sogari, Alberto, Emanuele Rovera, Nicole Megan Reilly, et al. "Abstract 5900: Tolerance to colibactin correlates with response to chemotherapeutic agents in colorectal cancer." Cancer Research 83, no. 7_Supplement (2023): 5900. http://dx.doi.org/10.1158/1538-7445.am2023-5900.

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Abstract Introduction: The bacterial genotoxin colibactin is enriched in colorectal cancer (CRC) and promotes the accumulation of mutations that drive tumorigenesis. However, systematic assessment of its impact on DNA damage response is lacking and the effect of colibactin exposure on response to other genotoxic agents (such as chemotherapy) is missing. Materials and Methods: We implemented an in vitro bacteria-coculture system to assess the effect of colibactin on a representative subset of 40 molecularly and pharmacologically annotated CRC cell lines and in a panel of isogenic DDR KO cell li

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Sogari, Alberto, Emanuele Rovera, Nicole Megan Reilly, et al. "Abstract B005: Tolerance to colibactin correlates with response to chemotherapeutic agents in colorectal cancer." Cancer Research 84, no. 1_Supplement (2024): B005. http://dx.doi.org/10.1158/1538-7445.dnarepair24-b005.

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Abstract Introduction. The bacterial genotoxin colibactin is enriched in colorectal cancer (CRC) and promotes the accumulation of mutations that drive tumorigenesis. However, systematic assessment of its impact on DNA damage response is lacking and the effect of colibactin exposure on response to other genotoxic agents (such as chemotherapy) is missing. Materials and methods: We implemented an in vitro bacteria-coculture system to assess the effect of colibactin on a representative subset of 40 molecularly and pharmacologically annotated CRC cell lines and in a panel of isogenic DDR KO cell li

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4

Wilson, Matthew R., Yindi Jiang, Peter W. Villalta, et al. "The human gut bacterial genotoxin colibactin alkylates DNA." Science 363, no. 6428 (2019): eaar7785. http://dx.doi.org/10.1126/science.aar7785.

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Certain Escherichia coli strains residing in the human gut produce colibactin, a small-molecule genotoxin implicated in colorectal cancer pathogenesis. However, colibactin’s chemical structure and the molecular mechanism underlying its genotoxic effects have remained unknown for more than a decade. Here we combine an untargeted DNA adductomics approach with chemical synthesis to identify and characterize a covalent DNA modification from human cell lines treated with colibactin-producing E. coli. Our data establish that colibactin alkylates DNA with an unusual electrophilic cyclopropane. We sho

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Dougherty, Michael W., and Christian Jobin. "Shining a Light on Colibactin Biology." Toxins 13, no. 5 (2021): 346. http://dx.doi.org/10.3390/toxins13050346.

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Colibactin is a secondary metabolite encoded by the pks gene island identified in several Enterobacteriaceae, including some pathogenic Escherichia coli (E. coli) commonly enriched in mucosal tissue collected from patients with inflammatory bowel disease and colorectal cancer. E. coli harboring this biosynthetic gene cluster cause DNA damage and tumorigenesis in cell lines and pre-clinical models, yet fundamental knowledge regarding colibactin function is lacking. To accurately assess the role of pks+ E. coli in cancer etiology, the biological mechanisms governing production and delivery of co

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6

Silpe, Justin E., Joel W. H. Wong, Siân V. Owen, Michael Baym, and Emily P. Balskus. "The bacterial toxin colibactin triggers prophage induction." Nature 603, no. 7900 (2022): 315–20. http://dx.doi.org/10.1038/s41586-022-04444-3.

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AbstractColibactin is a chemically unstable small-molecule genotoxin that is produced by several different bacteria, including members of the human gut microbiome1,2. Although the biological activity of colibactin has been extensively investigated in mammalian systems3, little is known about its effects on other microorganisms. Here we show that colibactin targets bacteria that contain prophages, and induces lytic development through the bacterial SOS response. DNA, added exogenously, protects bacteria from colibactin, as does expressing a colibactin resistance protein (ClbS) in non-colibactin

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7

Xue, Mengzhao, Chung Sub Kim, Alan R. Healy, et al. "Structure elucidation of colibactin and its DNA cross-links." Science 365, no. 6457 (2019): eaax2685. http://dx.doi.org/10.1126/science.aax2685.

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Colibactin is a complex secondary metabolite produced by some genotoxic gut Escherichia coli strains. The presence of colibactin-producing bacteria correlates with the frequency and severity of colorectal cancer in humans. However, because colibactin has not been isolated or structurally characterized, studying the physiological effects of colibactin-producing bacteria in the human gut has been difficult. We used a combination of genetics, isotope labeling, tandem mass spectrometry, and chemical synthesis to deduce the structure of colibactin. Our structural assignment accounts for all known b

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8

Hallam, Jennifer C., Sofia Sandalli, Iris Floria, et al. "D-Serine reduces the expression of the cytopathic genotoxin colibactin." Microbial Cell 10, no. 3 (2023): 63–77. http://dx.doi.org/10.15698/mic2023.03.793.

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Some Escherichia coli strains harbour the pks island, a 54 kb genomic island en-coding the biosynthesis genes for a genotoxic compound named colibactin. In eukaryotic cells, colibactin can induce DNA damage, cell cycle arrest and chro-mosomal instability. Production of colibactin has been implicated in the devel-opment of colorectal cancer (CRC). In this study, we demonstrate the inhibito-ry effect of D-Serine on the expression of the pks island in both prototypic and clinically-associated colibactin-producing strains and determine the implications for cytopathic effects on host cells. We also

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9

Nougayrede, J. P. "The genotoxin colibactin." Toxicon 116 (June 2016): 74–75. http://dx.doi.org/10.1016/j.toxicon.2016.01.012.

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10

Meng, Xia, Yanfei Chen, Peili Wang, et al. "Phosphopantetheinyl transferase ClbA contributes to the virulence of avian pathogenic Escherichia coli in meningitis infection of mice." PLOS ONE 17, no. 7 (2022): e0269102. http://dx.doi.org/10.1371/journal.pone.0269102.

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Avian pathogenic Escherichia coli (APEC), which has potential zoonotic risk, can cause severe systemic infections such as septicemia and meningitis in poultry. Colibactin is a hybrid non-ribosomal peptide/polyketide secondary metabolite produced by bacteria, which induces double-strand DNA breaks and chromosome instability in eukaryotic cells. ClbA is a 4’-phosphopantetheinyl transferase (PPTase) that is essential for colibactin and plays a role in siderophore synthesis. However, whether ClbA is associated with meningitis development in APEC is unclear. In this study, we abolished the clbA gen

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11

Engel, Philipp, Maria I. Vizcaino, and Jason M. Crawford. "Gut Symbionts from Distinct Hosts Exhibit Genotoxic Activity via Divergent Colibactin Biosynthesis Pathways." Applied and Environmental Microbiology 81, no. 4 (2014): 1502–12. http://dx.doi.org/10.1128/aem.03283-14.

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ABSTRACTSecondary metabolites produced by nonribosomal peptide synthetase (NRPS) or polyketide synthase (PKS) pathways are chemical mediators of microbial interactions in diverse environments. However, little is known about their distribution, evolution, and functional roles in bacterial symbionts associated with animals. A prominent example is colibactin, a largely unknown family of secondary metabolites produced byEscherichia colivia a hybrid NRPS-PKS biosynthetic pathway that inflicts DNA damage upon eukaryotic cells and contributes to colorectal cancer and tumor formation in the mammalian

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Oliero, M., R. Hajjar, T. Cuisiniere, G. Fragoso, A. Calvé, and M. M. Santos. "A270 THE PREBIOTIC, INULIN, IMPACTS TUMORIGENESIS PROMOTION BY COLIBACTIN-PRODUCING." Journal of the Canadian Association of Gastroenterology 6, Supplement_1 (2023): 86. http://dx.doi.org/10.1093/jcag/gwac036.270.

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Abstract Background The prebiotic inulin has previously shown both protective and tumor-promoting effects in colorectal cancer. These discrepancies may be due to polyketide synthase-positive (pks+) Escherichia coli promoting carcinogenesis through the production of colibactin, a genotoxin that induces double-strand DNA breaks (DSBs). Purpose In this study we investigated the impact of inulin on the genotoxicity of colibactin-producing bacteria. Method E. coli strains Nissle (EcN), and NC101 (EcNC101) were grown in medium supplemented with inulin. Colibactin expression was assessed by luciferas

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13

Putze, Johannes, Claire Hennequin, Jean-Philippe Nougayrède, et al. "Genetic Structure and Distribution of the Colibactin Genomic Island among Members of the Family Enterobacteriaceae." Infection and Immunity 77, no. 11 (2009): 4696–703. http://dx.doi.org/10.1128/iai.00522-09.

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ABSTRACT A genomic island encoding the biosynthesis and secretion pathway of putative hybrid nonribosomal peptide-polyketide colibactin has been recently described in Escherichia coli. Colibactin acts as a cyclomodulin and blocks the eukaryotic cell cycle. The origin and prevalence of the colibactin island among enterobacteria are unknown. We therefore screened 1,565 isolates of different genera and species related to the Enterobacteriaceae by PCR for the presence of this DNA element. The island was detected not only in E. coli but also in Klebsiella pneumoniae, Enterobacter aerogenes, and Cit

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14

Secher, Thomas, Delphine Payros, Camille Brehin, et al. "Oral Tolerance Failure upon Neonatal Gut Colonization with Escherichia coli Producing the Genotoxin Colibactin." Infection and Immunity 83, no. 6 (2015): 2420–29. http://dx.doi.org/10.1128/iai.00064-15.

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The intestinal barrier controls the balance between tolerance and immunity to luminal antigens. When this finely tuned equilibrium is deregulated, inflammatory disorders can occur. There is a concomitant increase, in urban populations of developed countries, of immune-mediated diseases along with a shift inEscherichia colipopulation from the declining phylogenetic group A to the newly dominant group B2, including commensal strains producing a genotoxin called colibactin that massively colonized the gut of neonates. Here, we showed that mother-to-offspring early gut colonization by colibactin-p

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15

Chagneau, Camille V., Clémence Massip, Nadège Bossuet-Greif, et al. "Uropathogenic E. coli induces DNA damage in the bladder." PLOS Pathogens 17, no. 2 (2021): e1009310. http://dx.doi.org/10.1371/journal.ppat.1009310.

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Urinary tract infections (UTIs) are among the most common outpatient infections, with a lifetime incidence of around 60% in women. We analysed urine samples from 223 patients with community-acquired UTIs and report the presence of the cleavage product released during the synthesis of colibactin, a bacterial genotoxin, in 55 of the samples examined. Uropathogenic Escherichia coli strains isolated from these patients, as well as the archetypal E. coli strain UTI89, were found to produce colibactin. In a murine model of UTI, the machinery producing colibactin was expressed during the early hours

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Wong, Jun Jie, Foo Kiong Ho, Pei Yi Choo, et al. "Escherichia coli BarA-UvrY regulates the pks island and kills Staphylococci via the genotoxin colibactin during interspecies competition." PLOS Pathogens 18, no. 9 (2022): e1010766. http://dx.doi.org/10.1371/journal.ppat.1010766.

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Wound infections are often polymicrobial in nature, biofilm associated and therefore tolerant to antibiotic therapy, and associated with delayed healing. Escherichia coli and Staphylococcus aureus are among the most frequently cultured pathogens from wound infections. However, little is known about the frequency or consequence of E. coli and S. aureus polymicrobial interactions during wound infections. Here we show that E. coli kills Staphylococci, including S. aureus, both in vitro and in a mouse excisional wound model via the genotoxin, colibactin. Colibactin biosynthesis is encoded by the p

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17

Gagnière, Johan, Virginie Bonnin, Anne-Sophie Jarrousse, et al. "Interactions between microsatellite instability and human gut colonization by Escherichia coli in colorectal cancer." Clinical Science 131, no. 6 (2017): 471–85. http://dx.doi.org/10.1042/cs20160876.

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Recent studies suggest that colonization of colonic mucosa by pathogenic Escherichia coli could be involved in the development of colorectal cancer (CRC), especially through the production of genotoxins such as colibactin and/or by interfering with the DNA mismatch repair (MMR) pathway that leads to microsatellite instability (MSI). The present study, performed on 88 CRC patients, revealed a significant increase in E. coli colonization in the MSI CRC phenotype. In the same way, E. coli persistence and internalization were increased in vitro in MMR-deficient cells. Moreover, we demonstrated tha

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18

Celia Henry Arnaud. "Colibactin activates latent viruses." C&EN Global Enterprise 100, no. 9 (2022): 12. http://dx.doi.org/10.1021/cen-10009-scicon4.

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19

Deane, Caitlin. "Colibactin comes to light." Nature Chemical Biology 15, no. 10 (2019): 933. http://dx.doi.org/10.1038/s41589-019-0373-8.

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McCarthy, Alex J., Patricia Martin, Emilie Cloup, Richard A. Stabler, Eric Oswald, and Peter W. Taylor. "The Genotoxin Colibactin Is a Determinant of Virulence in Escherichia coli K1 Experimental Neonatal Systemic Infection." Infection and Immunity 83, no. 9 (2015): 3704–11. http://dx.doi.org/10.1128/iai.00716-15.

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Escherichia colistrains expressing the K1 capsule are a major cause of sepsis and meningitis in human neonates. The development of these diseases is dependent on the expression of a range of virulence factors, many of which remain uncharacterized. Here, we show that all but 1 of 34E. coliK1 neonatal isolates carriedclbAandclbP, genes contained within thepkspathogenicity island and required for the synthesis of colibactin, a polyketide-peptide genotoxin that causes genomic instability in eukaryotic cells by induction of double-strand breaks in DNA. Inactivation ofclbAandclbPinE. coliA192PP, a v

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21

Van Lanen, Steven G. "SAM cycles up for colibactin." Nature Chemical Biology 13, no. 10 (2017): 1059–61. http://dx.doi.org/10.1038/nchembio.2479.

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22

Wernke, Kevin M., Mengzhao Xue, Alina Tirla, Chung Sub Kim, Jason M. Crawford, and Seth B. Herzon. "Structure and bioactivity of colibactin." Bioorganic & Medicinal Chemistry Letters 30, no. 15 (2020): 127280. http://dx.doi.org/10.1016/j.bmcl.2020.127280.

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23

Vizcaino, Maria I., and Jason M. Crawford. "The colibactin warhead crosslinks DNA." Nature Chemistry 7, no. 5 (2015): 411–17. http://dx.doi.org/10.1038/nchem.2221.

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24

Tariq, Habiba, Zobia Noreen, Aftab Ahmad, et al. "Colibactin possessing E. coli isolates in association with colorectal cancer and their genetic diversity among Pakistani population." PLOS ONE 17, no. 11 (2022): e0262662. http://dx.doi.org/10.1371/journal.pone.0262662.

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Colorectal cancer (CRC) is the third most prevalent cause of tumorigenesis and several pathogenic bacteria have been correlated with aggressive cases of cancer i.e., genotoxin (colibactin) producing Escherichia coli (E. coli). This study was designed to investigate the genetic diversity of clb+clb+ E. coli strains and their association with CRC. Pathogenic E. coli isolates from colorectal biopsies were characterized based on phylotypes, antibiotic resistance pattern, and (Enterobacterial Repetitive Intergenic Consensus Sequence-based Polymerase Chain Reaction) ERIC-PCR. Furthermore, isolates w

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Tang-Fichaux, Min, Priscilla Branchu, Jean-Philippe Nougayrède, and Eric Oswald. "Tackling the Threat of Cancer Due to Pathobionts Producing Colibactin: Is Mesalamine the Magic Bullet?" Toxins 13, no. 12 (2021): 897. http://dx.doi.org/10.3390/toxins13120897.

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Colibactin is a genotoxin produced primarily by Escherichia coli harboring the genomic pks island (pks+ E. coli). Pks+ E. coli cause host cell DNA damage, leading to chromosomal instability and gene mutations. The signature of colibactin-induced mutations has been described and found in human colorectal cancer (CRC) genomes. An inflamed intestinal environment drives the expansion of pks+ E. coli and promotes tumorigenesis. Mesalamine (i.e., 5-aminosalycilic acid), an effective anti-inflammatory drug, is an inhibitor of the bacterial polyphosphate kinase (PPK). This drug not only inhibits the p

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Tronnet, Sophie, Christophe Garcie, Nadine Rehm, Ulrich Dobrindt, Eric Oswald, and Patricia Martin. "Iron Homeostasis Regulates the Genotoxicity of Escherichia coli That Produces Colibactin." Infection and Immunity 84, no. 12 (2016): 3358–68. http://dx.doi.org/10.1128/iai.00659-16.

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The genotoxin colibactin is a secondary metabolite produced by a variety of pathogenic enterobacteria. Its biosynthesis requires the enzymatic activity of the phosphopantetheinyl transferase (PPTase) ClbA. We previously showed that ClbA can also contribute to the production of siderophores. Because the biosynthesis of siderophores is regulated by iron availability, we hypothesized that iron could also modulate the production of colibactin through the transcriptional regulation of clbA . This study revealed an increased transcription of clbA under iron-limiting conditions and a decrease of clbA

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Brachmann, A. O., C. Garcie, V. Wu, et al. "Colibactin biosynthesis and biological activity depend on the rare aminomalonyl polyketide precursor." Chemical Communications 51, no. 66 (2015): 13138–41. http://dx.doi.org/10.1039/c5cc02718g.

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28

Balskus, Emily P. "Colibactin: understanding an elusive gut bacterial genotoxin." Natural Product Reports 32, no. 11 (2015): 1534–40. http://dx.doi.org/10.1039/c5np00091b.

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29

Williams, Peyton C., Kevin M. Wernke, Alina Tirla, and Seth B. Herzon. "Employing chemical synthesis to study the structure and function of colibactin, a “dark matter” metabolite." Natural Product Reports 37, no. 11 (2020): 1532–48. http://dx.doi.org/10.1039/d0np00072h.

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30

Bian, Xiaoying, Alberto Plaza, Youming Zhang, and Rolf Müller. "Two more pieces of the colibactin genotoxin puzzle from Escherichia coli show incorporation of an unusual 1-aminocyclopropanecarboxylic acid moiety." Chemical Science 6, no. 5 (2015): 3154–60. http://dx.doi.org/10.1039/c5sc00101c.

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31

Mezerová, Kristýna, Lubomír Starý, Pavel Zbořil, et al. "Cyclomodulins and Hemolysis in E. coli as Potential Low-Cost Non-Invasive Biomarkers for Colorectal Cancer Screening." Life 11, no. 11 (2021): 1165. http://dx.doi.org/10.3390/life11111165.

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The frequent occurrence of E. coli positive for cyclomodulins such as colibactin (CLB), the cytotoxic necrotizing factor (CNF), and the cytolethal distending factor (CDT) in colorectal cancer (CRC) patients published so far provides the opportunity to use them as CRC screening markers. We examined the practicability and performance of a low-cost detection approach that relied on culture followed by simplified DNA extraction and PCR in E. coli isolates recovered from 130 CRC patients and 111 controls. Our results showed a statistically significant association between CRC and the presence of col

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Wang, Peili, Jiaxiang Zhang, Yanfei Chen, et al. "ClbG in Avian Pathogenic Escherichia coli Contributes to Meningitis Development in a Mouse Model." Toxins 13, no. 8 (2021): 546. http://dx.doi.org/10.3390/toxins13080546.

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Colibactin is a complex secondary metabolite that leads to genotoxicity that interferes with the eukaryotic cell cycle. It plays an important role in many diseases, including neonatal mouse sepsis and meningitis. Avian pathogenic Escherichia coli (APEC) is responsible for several diseases in the poultry industry and may threaten human health due to its potential zoonosis. In this study, we confirmed that clbG was necessary for the APEC XM strain to produce colibactin. The deletion of clbG on APEC XM contributed to lowered γH2AX expression, no megalocytosis, and no cell cycle arrest in vitro. N

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Gerstberger, Stefanie, Melissa Lumish, Saskia Hartner, et al. "Abstract 2796: Colibactin mutation signatures are associated with younger age of onset in colorectal cancer." Cancer Research 84, no. 6_Supplement (2024): 2796. http://dx.doi.org/10.1158/1538-7445.am2024-2796.

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Abstract Escherichia coli (E. coli) strains carrying the polyketide synthase (pks) island produce the genotoxin colibactin associated with pathogenesis of colorectal cancer (CRC). Colibactin binds directly to DNA, causing alkylating damage leading to double stranded DNA breaks. Colibactin mutagenesis results in mutations in hexameric A-T rich DNA motifs that can be identified by whole genome sequencing (WGS) as mutation signatures SBS28 and SBS88 (SBS-pks). Since WGS is not routinely used clinically, we developed an approach to specifically identify SBS-pks using a clinical targeted exon captu

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Salesse, Laurène, Cécily Lucas, My Hanh Thi Hoang, et al. "Colibactin-Producing Escherichia coli Induce the Formation of Invasive Carcinomas in a Chronic Inflammation-Associated Mouse Model." Cancers 13, no. 9 (2021): 2060. http://dx.doi.org/10.3390/cancers13092060.

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Background: Escherichia coli producing the genotoxin colibactin (CoPEC or colibactin-producing E. coli) abnormally colonize the colonic mucosa of colorectal cancer (CRC) patients. We previously showed that deficiency of autophagy in intestinal epithelial cells (IECs) enhances CoPEC-induced colorectal carcinogenesis in ApcMin/+ mice. Here, we tested if CoPEC trigger tumorigenesis in a mouse model lacking genetic susceptibility or the use of carcinogen. Methods: Mice with autophagy deficiency in IECs (Atg16l1∆IEC) or wild-type mice (Atg16l1flox/flox) were infected with the CoPEC 11G5 strain or t

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Valle-Encinas, Eider, Mayke Doorn, Farzin Pourfarzad, et al. "Abstract 242: Development of organoids-bacteria co-cultures for medium-to-high throughput screening." Cancer Research 84, no. 6_Supplement (2024): 242. http://dx.doi.org/10.1158/1538-7445.am2024-242.

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Abstract HUB patient derived organoids, (HUB-OrganoidsTM or PDOs) are self-organized epithelial cell structures with near-physiological features, extensively used to model aspects of cancer initiation and progression. Microinjection of colibactin-producing pks+ E. coli into the lumen of PDOs resulted in the appearance of two co-occurring mutational signatures identified in a subset of colorectal cancer (CRC) patients, demonstrating that pks+ E. coli plays a causative role in CRC development. The scalability of PDO bacteria microinjection is, however, limited and represent a bottleneck in the s

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Healy, Alan R., Herman Nikolayevskiy, Jaymin R. Patel, Jason M. Crawford, and Seth B. Herzon. "A Mechanistic Model for Colibactin-Induced Genotoxicity." Journal of the American Chemical Society 138, no. 48 (2016): 15563–70. http://dx.doi.org/10.1021/jacs.6b10354.

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Xue, Mengzhao, Kevin M. Wernke, and Seth B. Herzon. "Depurination of Colibactin-Derived Interstrand Cross-Links." Biochemistry 59, no. 7 (2020): 892–900. http://dx.doi.org/10.1021/acs.biochem.9b01070.

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Faïs, Tiphanie, Julien Delmas, Nicolas Barnich, Richard Bonnet, and Guillaume Dalmasso. "Colibactin: More Than a New Bacterial Toxin." Toxins 10, no. 4 (2018): 151. http://dx.doi.org/10.3390/toxins10040151.

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Moodie, Lindon W. K., Madlen Hubert, Xin Zhou, et al. "Photoactivated Colibactin Probes Induce Cellular DNA Damage." Angewandte Chemie 131, no. 5 (2018): 1431–35. http://dx.doi.org/10.1002/ange.201812326.

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Moodie, Lindon W. K., Madlen Hubert, Xin Zhou, et al. "Photoactivated Colibactin Probes Induce Cellular DNA Damage." Angewandte Chemie International Edition 58, no. 5 (2018): 1417–21. http://dx.doi.org/10.1002/anie.201812326.

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Valle-Encinas, Eider, Roshni Nair, Katerina Pisa, et al. "Abstract 5917: Development of a medium-to-high throughput organoid-bacteria co-culture platform for the assessment of host pathogen interaction." Cancer Research 83, no. 7_Supplement (2023): 5917. http://dx.doi.org/10.1158/1538-7445.am2023-5917.

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Abstract Pathogens such as colibactin-producing bacteria strains of the Enterobacteriaceae family are highly prevalent in the gut microbiota of colorectal cancer (CRC) patients. HUB patient derived Organoids, (HUB-OrganoidsTM or PDOs) are self-organized epithelial cell structures with near-physiological features, extensively used to model aspects of cancer initiation and progression. Studies conducted by Pleguezuelos-Manzanos et al. (2020) showed that repetitive cycles of colibactin-producing bacteria into the organoid lumen via microinjection, led to two co-occurring mutational signatures app

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Oliero, M., T. Cuisiniere, R. Hajjar, G. Fragoso, A. Calve, and M. M. Santos. "A42 INULIN PROMOTES POLYPS DEVELOPMENT IN APC MIN/+ MOUSE COLONIZED BY ESCHERICHIA COLI NC101." Journal of the Canadian Association of Gastroenterology 4, Supplement_1 (2021): 271–72. http://dx.doi.org/10.1093/jcag/gwab002.040.

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Abstract Background Colibactin is a genotoxin that induces double-strand DNA breaks and is produced by Escherichia coli strains harboring the pks island. Human and animal studies have shown that colibactin-producing gut bacteria promote carcinogenesis and facilitate the progression of colorectal cancer through cellular senescence and chromosomal abnormalities. Aims In this study, we investigated the impact of inulin, a prebiotic able to modulate bacterial metabolism, in a colorectal cancer model, ApcMin/+mice, colonized by colibactin-producing E. coli strain NC101. Material & methods Apc M

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Zhou, Tao, Yuichiro Hirayama, Yuta Tsunematsu, et al. "Isolation of New Colibactin Metabolites from Wild-Type Escherichia coli and In Situ Trapping of a Mature Colibactin Derivative." Journal of the American Chemical Society 143, no. 14 (2021): 5526–33. http://dx.doi.org/10.1021/jacs.1c01495.

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Bossuet-Greif, Nadège, Damien Dubois, Claude Petit, et al. "Escherichia coli ClbS is a colibactin resistance protein." Molecular Microbiology 99, no. 5 (2015): 897–908. http://dx.doi.org/10.1111/mmi.13272.

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Arthur, Janelle C. "Microbiota and colorectal cancer: colibactin makes its mark." Nature Reviews Gastroenterology & Hepatology 17, no. 6 (2020): 317–18. http://dx.doi.org/10.1038/s41575-020-0303-y.

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He, Wencan, Lamia Azzi-Martin, Valérie Velasco, et al. "The CDT of Helicobacter hepaticus induces pro-survival autophagy and nucleoplasmic reticulum formation concentrating the RNA binding proteins UNR/CSDE1 and P62/SQSTM1." PLOS Pathogens 17, no. 3 (2021): e1009320. http://dx.doi.org/10.1371/journal.ppat.1009320.

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Humans are frequently exposed to bacterial genotoxins of the gut microbiota, such as colibactin and cytolethal distending toxin (CDT). In the present study, whole genome microarray-based identification of differentially expressed genes was performed in vitro on HT29 intestinal cells while following the ectopic expression of the active CdtB subunit of Helicobacter hepaticus CDT. Microarray data showed a CdtB-dependent upregulation of transcripts involved in positive regulation of autophagy concomitant with the downregulation of transcripts involved in negative regulation of autophagy. CdtB prom

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Khaertynov, Kh S., V. A. Anohin, A. A. Rizvanov, et al. "VIRULENCE AND ANTIBIOTIC RESISTANCE OF ISOLATES OF KLEBSIELLA PNEUMONIAE IN NEWBORNS WITH LOCALIZED AND GENERALIZED FORMS OF INFECTION." Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics) 63, no. 5 (2018): 139–46. http://dx.doi.org/10.21508/1027-4065-2018-63-5-139-146.

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Objective.To study the effect of virulence and antibiotic sensitivity of K. pneumoniae on the course and outcome of localized and generalized forms of infection in newborns.The authors studied 25 samples of K. pneumoniae isolated from the blood (12 isolates) and feces (13 isolates) of the children with various forms of neonatal infection. Group 1 consisted of 12 children with bacteriologically proven neonatal sepsis, K. pneumoniae was isolated of their blood. Group 2 included 13 children with localized bacterial infection in the form of pneumonia, K. pneumoniae was isolated from their feces. T

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Azour, Adel, Charbel Al-Bayssari, Lucile Pinault, Saïd Azza, Jean-Marc Rolain та Seydina M. Diene. "clbP Gene, a Potential New Member of the β-Lactamase Family". International Journal of Molecular Sciences 23, № 24 (2022): 15642. http://dx.doi.org/10.3390/ijms232415642.

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The colibactin island (pks) of Escherichia coli formed by 19 genes (55-Kb), encodes non-ribosomal peptide (NRP) and polyketide (PK) synthases, which allow the synthesis of colibactin, a suspected hybrid PK-NRP compound that causes damage to DNA in eukaryotic cells. The clbP, an unusual essential gene, is found in the operon structure with the clbS gene in the pks-encoded machinery. Interestingly, the clbP gene has been annotated as a β-lactamase but no previous study has reported its β-lactamase characteristics. In this study, we (i) investigated the β-lactamase properties of the clbP gene in

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Kalantari, Aida, Michael J. James, Lauren A. Renaud, et al. "Robust performance of a live bacterial therapeutic chassis lacking the colibactin gene cluster." PLOS ONE 18, no. 2 (2023): e0280499. http://dx.doi.org/10.1371/journal.pone.0280499.

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E. coli Nissle (EcN) is a non-pathogenic probiotic bacterium of the Enterobacteriaceae family that has been used for over a century to promote general gut health. Despite the history of safe usage of EcN, concerns have been raised regarding the presence of the pks gene cluster, encoding the genotoxin colibactin, due to its association with colorectal cancer. Here, we sought to determine the effect of pks island removal on the in vitro and in vivo robustness and activity of EcN and EcN-derived strains. A deletion of the pks island (Δpks) was constructed in wild type and engineered strains of Ec

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Tripathi, Prabhanshu, Emilee E. Shine, Alan R. Healy, et al. "ClbS Is a Cyclopropane Hydrolase That Confers Colibactin Resistance." Journal of the American Chemical Society 139, no. 49 (2017): 17719–22. http://dx.doi.org/10.1021/jacs.7b09971.

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