Escherichia coli and colorectal cancer: Unfolding the enigmatic relationship

2021 ◽  
Vol 22 ◽  
Author(s):  
Rogayeh Nouri ◽  
Alka Hasani ◽  
Kourosh Masnadi Shirazi ◽  
Mohammad Reza Aliand ◽  
Bita Sepehri ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Escherichia Coli ◽  
Mammalian Cells ◽  
Chromosomal Rearrangements ◽  
Current Evidence ◽  
Dna Breaks ◽  
Colon Cells ◽  
E Coli ◽  
Dna Mismatch ◽  
Double Strand Dna Breaks

: Colorectal cancer (CRC) is one of the deadliest cancers in the world. Specific strains of intestinal Escherichia coli (E. coli) may influence the initiation and development of CRC by exploiting virulence factors and inflammatory pathways. Mucosa-associated E. coli strains are more prevalent in CRC biopsies in comparison to healthy controls. Moreover, these strains can survive and replicate within macrophages and induce a pro-inflammatory response. Chronic exposure to inflammatory mediators can lead to increased cell proliferation and cancer. Production of colobactin toxin by the majority of mucosa-associated E. coli isolated from CRC patients is another notable finding. Colibactin-producing E. coli strains, in particular, induce double-strand DNA breaks, stop the cell cycle, involve in chromosomal rearrangements of mammalian cells and are implicated in carcinogenic effects in animal models. Moreover, some enteropathogenic E. coli (EPEC) strains are able to survive and replicate in colon cells as chronic intracellular pathogens and may promote susceptibility to CRC by downregulation of DNA Mismatch Repair (MMR) proteins. In this review, we discuss current evidence and focus on the mechanisms by which E. coli can influence the development of CRC.

scholarly journals A42 INULIN PROMOTES POLYPS DEVELOPMENT IN APC MIN/+ MOUSE COLONIZED BY ESCHERICHIA COLI NC101

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 271-272
Author(s):  
M Oliero ◽  
T Cuisiniere ◽  
R Hajjar ◽  
G Fragoso ◽  
A Calve ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Escherichia Coli ◽  
Animal Studies ◽  
Chromosomal Abnormalities ◽  
Coli Strain ◽  
Dna Breaks ◽  
E Coli ◽  
Double Strand Dna Breaks ◽  
The Impact

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 Min/+ mice were subjected to oral gavage with PBS (control) or 108 cfu of E. coli NC101 after a week of receiving a 2% dextran sulfate sodium solution in drinking water. Mice were fed a diet supplemented with 10% cellulose (control) or 10% inulin for 4 weeks. During necropsy, the number of polyps in the duodenum, jejunum, ileum, and colon was counted. Tumors in the colon were graded and the erythroid parameters were measured. Results We showed that the inulin diet increased the number of polyps in the ileum compared to cellulose. Moreover, mice colonized with E. coli NC101 and on the inulin diet presented severe anemia associated with an increasing number of polyps in the duodenum, jejunum, and ileum compared to mice supplemented with cellulose. Conclusions Our results suggest that, in vivo, inulin promotes polyp development in the small intestine of ApcMin/+ mice colonized by pks+ E. coli strain NC101. Funding Agencies CIHRNSERC

Interactions between microsatellite instability and human gut colonization by Escherichia coli in colorectal cancer

2017 ◽  
Vol 131 (6) ◽  
pp. 471-485 ◽  
Author(s):  
Johan Gagnière ◽  
Virginie Bonnin ◽  
Anne-Sophie Jarrousse ◽  
Emilie Cardamone ◽  
Allison Agus ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Escherichia Coli ◽  
Microsatellite Instability ◽  
Colorectal Carcinogenesis ◽  
E Coli ◽  
Dna Mismatch ◽  
Gut Colonization ◽  
Pathogenic Escherichia Coli ◽  
Mmr Proteins

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 that colibactin-producing E. coli induce inhibition of the mutL homologue 1 (MLH1) MMR proteins, which could lead to genomic instability. However, colibactin-producing E. coli were more frequently identified in microsatellite stable (MSS) CRC. The present study suggests differences in the involvement of colibactin-producing E. coli in colorectal carcinogenesis according to the CRC phenotype. Further host–pathogen interactions studies should take into account CRC phenotypes.

scholarly journals Inulin and Galacto-oligosaccharides Increase the Genotoxic Effect of Colibactin Produced by pks+ Escherichia Coli Strains

2020 ◽  
Author(s):  
Manon Oliero ◽  
Annie Calvé ◽  
Gabriela Fragoso ◽  
Thibault Cuisiniere ◽  
Roy Hajjar ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Chromosomal Abnormalities ◽  
Iron Sulfate ◽  
Luciferase Reporter ◽  
Dna Breaks ◽  
E Coli ◽  
Double Strand Dna Breaks ◽  
The Impact ◽  
Double Strand Dna

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 enhance the progression of colorectal cancer through cellular senescence and chromosomal abnormalities. In this study, we investigated the impact of prebiotics on the genotoxicity of colibactin-producing E. coli strains Nissle 1917 and NC101. Methods: Bacteria were grown in medium supplemented with 20, 30 and 40 mg/mL of prebiotics inulin or galacto-oligosaccharide, and with or without 5 µM, 25 µM and 125 µM of iron sulfate. Colibactin expression was assessed by luciferase reporter assay for the clbA gene, essential for colibactin production, in E. coli Nissle 1917 and by RT-PCR in E. coli NC101. The human epithelial colorectal adenocarcinoma cell line, Caco-2, was used to assess colibactin-induced megalocytosis by methylene blue binding assay and genotoxicity by γ-H2AX immunofluorescence analysis. Results: Inulin and galacto-oligosaccharide enhanced the expression of clbA in pks+ E. coli. However, the addition of 125 µM of iron sulfate inhibited the expression of clbA triggered by oligosaccharides. In the presence of either oligosaccharide, E. coli NC101 increased dysplasia and double-strand DNA breaks in Caco-2 cells compared to untreated cells. Conclusion: Our results suggest that, in vitro, prebiotic oligosaccharides exacerbate DNA damage induced by colibactin-producing bacteria. Further studies are necessary to establish whether these results are reproducible in vivo.

Sperm DNA Fragmentation

2021 ◽  
Author(s):  
Stamatios Karavolos
Keyword(s):  
Dna Fragmentation ◽  
Current Data ◽  
Low Fertility ◽  
Current Evidence ◽  
Sperm Dna Fragmentation ◽  
Dna Breaks ◽  
Dna Quality ◽  
Double Strand Dna Breaks ◽  
Sperm Dna ◽  
Clinically Significant

AbstractSperm DNA fragmentation refers to the accumulation of adducts as well as single- or double-strand DNA breaks and reflects the sperm DNA quality. Current data suggest that there are differences in sperm DNA quality among individuals with high or low fertility, and this observation has led to the idea that testing sperm DNA fragmentation could be a useful test of male fertility. However, sperm DNA fragmentation has become one of the most frequently debated topics in reproductive medicine, as there is no agreement about the optimal way to test for DNA fragmentation, the clinically significant level of sperm DNA fragmentation, as well as the best therapeutic options for infertile men. This article presents current evidence related to sperm DNA fragmentation and its role in managing male infertility.

scholarly journals Target-AID-Mediated Multiplex Base Editing in Porcine Fibroblasts

2021 ◽  
Author(s):  
Soo-Young Yum ◽  
Goo Jang ◽  
Okjae Koo
Keyword(s):  
Genome Editing ◽  
Cytidine Deaminase ◽  
Chromosomal Rearrangements ◽  
Dna Breaks ◽  
Base Editing ◽  
Multiple Loci ◽  
Double Strand Dna Breaks ◽  
Protospacer Adjacent Motif ◽  
Motif Site ◽  
Programmable Nucleases

Multiplex genome editing may induce genotoxicity and chromosomal rearrangements due to double-strand DNA breaks at multiple loci simultaneously induced by programmable nucleases, including CRISPR/Cas9. However, recently developed base-editing systems can directly substitute target sequences without double-strand breaks. Thus, the base-editing system is expected to be a safer method for multiplex genome-editing platforms for livestock. Target-AID is a base editing system composed of PmCDA1, a cytidine deaminase from sea lampreys, fused to Cas9 nickase. It can be used to substitute cytosine for thymine in 3-5 base editing windows, 18 bases upstream of the protospacer-adjacent motif site. In the current study, we demonstrated Target-AID-mediated base editing in porcine cells for the first time. We targeted multiple loci in the porcine genome using the Target-AID system and successfully induced target-specific base substitutions with up to 63.15% efficiency. This system can be used for the further production of various genome-engineered pigs.

scholarly journals E1A 13S and 12S mRNA products made in Escherichia coli both function as nucleus-localized transcription activators but do not directly bind DNA.

1985 ◽  
Vol 5 (10) ◽  
pp. 2653-2661 ◽  
Author(s):  
B Ferguson ◽  
B Krippl ◽  
O Andrisani ◽  
N Jones ◽  
H Westphal ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Mammalian Cells ◽  
Biochemical Properties ◽  
Protein Product ◽  
Gene Products ◽  
E Coli ◽  
Adenovirus E1a ◽  
Myc Gene ◽  
E1a Gene ◽  
Transcription Activators

We previously purified and characterized functionally the Escherichia coli-expressed product of the human subgroup C adenovirus E1A 13S mRNA (B. Ferguson, N. Jones, J. Richter, and M. Rosenberg, Science 224:1343-1346, 1984; B. Krippl, B. Ferguson, M. Rosenberg, and H. Westphal, Proc. Natl. Acad. Sci. USA 81:6988-6992, 1984). We have now expressed in E. coli and purified the protein product encoded by the human subgroup C adenovirus E1A 12S mRNA and have compared the functional properties of this protein with those of the E1A 13S mRNA product. Using microinjection techniques to introduce these proteins into mammalian cells, we found that the E1A 12S mRNA product, like the 13S mRNA product, localized rapidly to the cell nucleus and induced adenovirus gene expression. Although both E1A gene products localized to the nucleus and stimulated adenovirus gene transcription, these proteins did not directly bind to DNA under conditions in which a known DNA-binding protein, the human c-myc gene product, bound DNA efficiently. Thus, the E1A and myc gene products, which have been related both structurally and functionally, exhibit distinctly different biochemical properties.

scholarly journals Novel Roles for the AIDA Adhesin from Diarrheagenic Escherichia coli: Cell Aggregation and Biofilm Formation

2004 ◽  
Vol 186 (23) ◽  
pp. 8058-8065 ◽  
Author(s):  
Orla Sherlock ◽  
Mark A. Schembri ◽  
Andreas Reisner ◽  
Per Klemm
Keyword(s):  
Escherichia Coli ◽  
Biofilm Formation ◽  
Mammalian Cells ◽  
Gastrointestinal Disease ◽  
Cell Aggregation ◽  
Bacterial Attachment ◽  
E Coli ◽  
Abiotic Surfaces ◽  
Broad Variety ◽  
Self Association

ABSTRACT Diarrhea-causing Escherichia coli strains are responsible for numerous cases of gastrointestinal disease and constitute a serious health problem throughout the world. The ability to recognize and attach to host intestinal surfaces is an essential step in the pathogenesis of such strains. AIDA is a potent bacterial adhesin associated with some diarrheagenic E. coli strains. AIDA mediates bacterial attachment to a broad variety of human and other mammalian cells. It is a surface-displayed autotransporter protein and belongs to the selected group of bacterial glycoproteins; only the glycosylated form binds to mammalian cells. Here, we show that AIDA possesses self-association characteristics and can mediate autoaggregation of E. coli cells. We demonstrate that intercellular AIDA-AIDA interaction is responsible for bacterial autoaggregation. Interestingly, AIDA-expressing cells can interact with antigen 43 (Ag43)-expressing cells, which is indicative of an intercellular AIDA-Ag43 interaction. Additionally, AIDA expression dramatically enhances biofilm formation by E. coli on abiotic surfaces in flow chambers.

scholarly journals Amber suppression in mammalian cells dependent upon expression of an Escherichia coli aminoacyl-tRNA synthetase gene.

1996 ◽  
Vol 16 (3) ◽  
pp. 907-913 ◽  
Author(s):  
H J Drabkin ◽  
H J Park ◽  
U L RajBhandary
Keyword(s):  
Escherichia Coli ◽  
Mammalian Cells ◽  
Trna Gene ◽  
Trna Synthetase ◽  
Developmentally Regulated ◽  
Coding Sequence ◽  
Suppressor Trna ◽  
Trna Synthetases ◽  
E Coli ◽  
Nonsense Codons

As an approach to inducible suppression of nonsense mutations in mammalian and in higher eukaryotic cells, we have analyzed the expression of an Escherichia coli glutamine-inserting amber suppressor tRNA gene in COS-1 and CV-1 monkey kidney cells. The tRNA gene used has the suppressor tRNA coding sequence flanked by sequences derived from a human initiator methionine tRNA gene and has two changes in the coding sequence. This tRNA gene is transcribed, and the transcript is processed to yield the mature tRNA in COS-1 and CV-1 cells. We show that the tRNA is not aminoacylated in COS-1 cells by any of the endogenous aminoacyl-tRNA synthetases and is therefore not functional as a suppressor. Concomitant expression of the E. coli glutaminyl-tRNA synthetase gene results in aminoacylation of the suppressor tRNA and its functioning as a suppressor. These results open up the possibility of attempts at regulated suppression of nonsense codons in mammalian cells by regulating expression of the E. coli glutaminyl-tRNA synthetase gene in an inducible, cell-type specific, or developmentally regulated manner.

scholarly journals Transcription of brain chromatin by ribonucleic acid polymerases from brain nucleic and from Escherichia coli

1972 ◽  
Vol 130 (4) ◽  
pp. 1095-1099 ◽  
Author(s):  
Vijendra K. Singh ◽  
S. C. Sung
Keyword(s):  
Escherichia Coli ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Mammalian Cells ◽  
Transcriptional Control ◽  
Polymerase Activity ◽  
Control Mechanisms ◽  
E Coli ◽  
Bacterial Enzyme ◽  
Rna Polymerase Activity

1. Transcription of ox brain chromatin by brain nuclear RNA polymerase II and Escherichia coli RNA polymerase was studied. 2. The soluble chromatin prepared from brain nuclei contained DNA, RNA, histone and non-histone proteins. Such chromatin preparations did not display any endogenous RNA polymerase activity, when assayed in the presence of concentrations of KCl as high as 0.4m. 3. The chromatin-templated activity of brain nuclear polymerase II was stimulated by KCl, with an optimum around 0.25m. 4. The template activity of brain chromatin for brain nuclear polymerase II and E. coli enzyme was about 20–25% of that of pure DNA. This greatly repressed templatecapacity of chromatin was probably due to the acid-soluble chromosomal proteins. 5. Brain nuclear polymerase II was 3–4 times more active with dehistonized chromatin than with pure DNA as template, whereas bacterial enzyme was almost equally active with either of these two templates, reflecting the specificity of the transcriptional control mechanisms in mammalian cells.

scholarly journals Pks+ Escherichia Coli More Prevalent in Benign than Malignant Colorectal Tumors

2021 ◽  
Author(s):  
Carmina Villariba Tolentino ◽  
Ana Maria Cariño ◽  
Kin Israel Notarte ◽  
Imee Macaranas ◽  
Allan Fellizar ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Escherichia Coli ◽  
Malignant Tumors ◽  
Colorectal Tumors ◽  
Tissue Samples ◽  
E Coli ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Formalin Fixed

Abstract Background: Some E. coli strains that synthesize the toxin colibactin within the 54-kb pks island are being implicated in colorectal cancer (CRC) development. Here, the prevalence of pks+ E. coli in malignant and benign colorectal tumors obtained from selected Filipino patients was compared to determine the association of pks+ E. coli with CRC in this population. Methods and Results: A realtime qPCR protocol was developed to quantify uidA, clbB, clbN, and clbA genes in formalin fixed paraffin embedded colorectal tissues. The number of malignant tumors (44/62; 71%) positive for the uidA gene was not significantly different (p=0.3428) from benign (38/62; 61%) tumors. Significantly higher number of benign samples (p<0.05) were positive for all three colibactin genes (clbB, clbN, and clbA) compared with malignant samples. There was also higher prevalence of pks+ E. coli among older females and in tissue samples taken from the rectum. Conclusion: Hence, pks+ E. coli may not be associated with CRC development among Filipinos.

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