scholarly journals Shining a Light on Colibactin Biology

Toxins ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 346
Author(s):  
Michael W. Dougherty ◽  
Christian Jobin
Keyword(s):  
Biosynthetic Gene Cluster ◽  
Cancer Etiology ◽  
Mutagenic Potential ◽  
E Coli ◽  
Pathogenic Escherichia Coli ◽  
Clinical Models ◽  
Inflammatory Bowel ◽  
Structural Mode ◽  
Gene Island

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 colibactin by these bacteria must be elucidated. In this review, we will focus on recent advances in our understanding of colibactin’s structural mode-of-action and mutagenic potential with consideration for how this activity may be regulated by physiologic conditions within the intestine.

scholarly journals Role of Virulence Factors in Resistance of Avian Pathogenic Escherichia coli to Serum and in Pathogenicity

2003 ◽  
Vol 71 (1) ◽  
pp. 536-540 ◽  
Author(s):  
Melha Mellata ◽  
Maryvonne Dho-Moulin ◽  
Charles M. Dozois ◽  
Roy Curtiss ◽  
Peter K. Brown ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Virulence Factors ◽  
Bacterial Resistance ◽  
Serum Resistance ◽  
Temperature Sensitive ◽  
E Coli ◽  
Pathogenic Escherichia Coli ◽  
K1 Capsule

ABSTRACT In chickens, colibacillosis is caused by avian pathogenic Escherichia coli (APEC) via respiratory tract infection. Many virulence factors, including type 1 (F1A) and P (F11) fimbriae, curli, aerobactin, K1 capsule, and temperature-sensitive hemagglutinin (Tsh) and plasmid DNA regions have been associated with APEC. A strong correlation between serum resistance and virulence has been demonstrated, but roles of virulence factors in serum resistance have not been well elucidated. By using mutants of APEC strains TK3, MT78, and χ7122, which belong to serogroups O1, O2, and O78, respectively, we investigated the role of virulence factors in resistance to serum and pathogenicity in chickens. Our results showed that serum resistance is one of the pathogenicity mechanisms of APEC strains. Virulence factors that increased bacterial resistance to serum and colonization of internal organs of infected chickens were O78 lipopolysaccharide of E. coli χ7122 and the K1 capsule of E. coli MT78. In contrast, curli, type 1, and P fimbriae did not appear to contribute to serum resistance. We also showed that the iss gene, which was previously demonstrated to increase resistance to serum in certain E. coli strains, is located on plasmid pAPEC-1 of E. coli χ7122 but does not play a major role in resistance to serum for strain χ7122.

scholarly journals Transcription Regulator YgeK Affects the Virulence of Avian Pathogenic Escherichia coli

Animals ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 3018
Author(s):  
Jian Tu ◽  
Dandan Fu ◽  
Yi Gu ◽  
Ying Shao ◽  
Xiangjun Song ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Transcriptional Regulator ◽  
Avian Pathogenic Escherichia Coli ◽  
E Coli ◽  
Pathogenic Escherichia Coli ◽  
System 2 ◽  
Important Regulator ◽  
Alignment Analysis ◽  
Responsible Pathogen

Avian pathogenic Escherichia coli (APEC) is the responsible pathogen for colibacillosis in poultry, and is a potential gene source for human extraintestinal pathogenic Escherichia coli. Escherichia coli type III secretion system 2 (ETT2) is widely distributed in human and animal ExPEC isolates, and is crucial for the virulence of ExPEC. Transcriptional regulator YgeK, located in the ETT2 gene cluster, was identified as an important regulator of gene expression in enterohemorrhagic E. coli (EHEC). However, the role of YgeK in APEC has not been reported. In this study, we performed amino acid alignment analysis of YgeK among different E. coli strains and generated ygeK mutant strain AE81ΔygeK from clinical APEC strain AE81. Flagellar formation, bacterial motility, serum sensitivity, adhesion, and virulence were all significantly reduced following the inactivation of YgeK in APEC. Then, we performed transcriptome sequencing to analyze the functional pathways involved in the biological processes. Results suggested that ETT2 transcriptional regulator YgeK plays a crucial role in APEC virulence. These findings thus contribute to our understanding of the function of the ETT2 cluster, and clarify the pathogenic mechanism of APEC.

scholarly journals Pathogenic Escherichia coli – virulence mechanisms

2016 ◽  
Vol 72 (6) ◽  
pp. 352-357
Author(s):  
Katarzyna Półtorak ◽  
Kinga Wieczorek ◽  
Jacek Osek
Keyword(s):  
Bloodstream Infections ◽  
Epidemiological Data ◽  
Intestinal Epithelial ◽  
Bacterial Strains ◽  
Internal Organs ◽  
E Coli ◽  
Cellular Processes ◽  
Pathogenic Escherichia Coli ◽  
Different Strains

E. coli are the predominant microorganisms in the human gastrointestinal tract. In most cases, they exist as harmless comensals, and some of them are beneficial to their host in balancing gut flora and absorption of nutrients. However, there are pathogenic strains that cause a broad range of diseases in humans and animals, from diarrhea to bloodstream infections. Among bacterial strains causing these symptoms, seven pathotypes are now recognized: enteropathogenic E. coli (EPEC), shiga toxin-producing E. coli (STEC), enterotoxigenic E. coli (ETEC), enteroinvasive E. coli (EIEC), enteroaggregative E. coli (EAEC), diffusely adherent E. coli (DAEC), and adherent-invasive E. coli (AIEC). Several different strains cause diverse diseases by means of virulence factors that facilitate their interactions with the host, including colonization of the intestinal epithelial surfaces, crossing of the mucosal barriers, invasion of the bloodstream and internal organs or producing toxins that affect various cellular processes. Pathogenic E. coli are commonly studied in humans, animals, food and the environment, in developed and developing countries. The presented paper reviews recent information concerning the pathogenic mechanisms of E. coli, the role of animals and food in the transmission chain and a short overview of epidemiological data.

scholarly journals Tackling the Threat of Cancer Due to Pathobionts Producing Colibactin: Is Mesalamine the Magic Bullet?

Toxins ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 897
Author(s):  
Min Tang-Fichaux ◽  
Priscilla Branchu ◽  
Jean-Philippe Nougayrède ◽  
Eric Oswald
Keyword(s):  
Colorectal Cancer ◽  
Intestinal Inflammation ◽  
Gene Mutations ◽  
Magic Bullet ◽  
Induced Mutations ◽  
Human Colorectal Cancer ◽  
E Coli ◽  
Bowel Diseases ◽  
Inflammatory Bowel

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 production of intestinal inflammatory mediators and the proliferation of CRC cells, but also limits the abundance of E. coli in the gut microbiota and diminishes the production of colibactin. Here, we describe the link between intestinal inflammation and colorectal cancer induced by pks+ E. coli. We discuss the potential mechanisms of the pleiotropic role of mesalamine in treating both inflammatory bowel diseases and reducing the risk of CRC due to pks+ E. coli.

Properties of haemolysin E (HlyE) from a pathogenic Escherichia coli avian isolate and studies of HlyE export

Microbiology ◽  
2004 ◽  
Vol 150 (5) ◽  
pp. 1495-1505 ◽  
Author(s):  
Neil R. Wyborn ◽  
Angela Clark ◽  
Ruth E. Roberts ◽  
Stuart J. Jamieson ◽  
Svetomir Tzokov ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Blood Cells ◽  
Cell Envelope ◽  
Membrane Integrity ◽  
Intrinsic Property ◽  
E Coli ◽  
Pathogenic Escherichia Coli ◽  
Carboxyl Terminal ◽  
K 12

Haemolysin E (HlyE) is a novel pore-forming toxin first identified in Escherichia coli K-12. Analysis of the 3-D structure of HlyE led to the proposal that a unique hydrophobic β-hairpin structure (the β-tongue, residues 177–203) interacts with the lipid bilayer in target membranes. In seeming contradiction to this, the hlyE sequence from a pathogenic E. coli strain (JM4660) that lacks all other haemolysins has been reported to encode an Arg residue at position 188 that was difficult to reconcile with the proposed role of the β-tongue. Here it is shown that the JM4660 hlyE sequence encodes Gly, not Arg, at position 188 and that substitution of Gly188 by Arg in E. coli K-12 HlyE abolishes activity, emphasizing the importance of the head domain in HlyE function. Nevertheless, 76 other amino acid substitutions were confirmed compared to the HlyE protein of E. coli K-12. The JM4660 HlyE protein was dimeric, suggesting a mechanism for improving toxin solubility, and it lysed red blood cells from many species by forming 36–41 Å diameter pores. However, the haemolytic phenotype of JM4660 was found to be unstable due to defects in HlyE export, indicating that export of active HlyE is not an intrinsic property of the protein but requires additional components. TnphoA mutagenesis of hlyE shows that secretion from the cytoplasm to the periplasm does not require the carboxyl-terminal region of HlyE. Finally, disruption of genes associated with cell envelope function, including tatC, impairs HlyE export, indicating that outer membrane integrity is important for effective HlyE secretion.

scholarly journals Role of Deoxyribose Catabolism in Colonization of the Murine Intestine by Pathogenic Escherichia coli Strains

2009 ◽  
Vol 77 (4) ◽  
pp. 1442-1450 ◽  
Author(s):  
Vanessa Martinez-Jéhanne ◽  
Laurence du Merle ◽  
Christine Bernier-Fébreau ◽  
Codruta Usein ◽  
Amy Gassama-Sow ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Biochemical Characterization ◽  
Pathogenic Potential ◽  
E Coli ◽  
Intestinal Epithelia ◽  
Gut Colonization ◽  
Pathogenic Escherichia Coli ◽  
Increased Risk ◽  
Evolutionary Step

ABSTRACT We previously suggested that the ability to metabolize deoxyribose, a phenotype encoded by the deoK operon, is associated with the pathogenic potential of Escherichia coli strains. Carbohydrate metabolism is thought to provide the nutritional support required for E. coli to colonize the intestine. We therefore investigated the role of deoxyribose catabolism in the colonization of the gut, which acts as a reservoir, by pathogenic E. coli strains. Molecular and biochemical characterization of 1,221 E. coli clones from various collections showed this biochemical trait to be common in the E. coli species (33.6%). However, multivariate analysis evidenced a higher prevalence of sugar-metabolizing E. coli clones in the stools of patients from countries in which intestinal diseases are endemic. Diarrhea processes frequently involve the destruction of intestinal epithelia, so it is plausible that such clones may be positively selected for in intestines containing abundant DNA, and consequently deoxyribose. Statistical analysis also indicated that symptomatic clinical disorders and the presence of virulence factors specific to extraintestinal pathogenic E. coli were significantly associated with an increased risk of biological samples and clones testing positive for deoxyribose. Using the streptomycin-treated-mouse model of intestinal colonization, we demonstrated the involvement of the deoK operon in gut colonization by two pathogenic isolates (one enteroaggregative and one uropathogenic strain). These results, indicating that deoxyribose availability promotes pathogenic E. coli growth during host colonization, suggest that the acquisition of this trait may be an evolutionary step enabling these pathogens to colonize and persist in the mammalian intestine.

scholarly journals The Final Step of Hygromycin A Biosynthesis, Oxidation of C-5″-Dihydrohygromycin A, Is Linked to a Putative Proton Gradient-Dependent Efflux

2009 ◽  
Vol 53 (12) ◽  
pp. 5163-5172 ◽  
Author(s):  
Vidya Dhote ◽  
Agata L. Starosta ◽  
Daniel N. Wilson ◽  
Kevin A. Reynolds
Keyword(s):  
Biosynthetic Pathway ◽  
High Titer ◽  
Biosynthetic Gene Cluster ◽  
Proton Gradient ◽  
Purification And Characterization ◽  
E Coli ◽  
Reduced Activity

ABSTRACT Hygromycin A (HA) is an aminocyclitol antibiotic produced and excreted by Streptomyces hygroscopicus. Deletion of hyg26 from the hygromycin A biosynthetic gene cluster has previously been shown to result in a mutant that produces 5″-dihydrohygromycin A (DHHA). We report herein on the purification and characterization of Hyg26 expressed in E scherichia coli. The enzyme catalyzes an NAD(H)-dependent reversible interconversion of HA and DHHA, supporting the role of the reduced HA as the penultimate biosynthetic pathway intermediate and not a shunt product. The equilibrium for the Hyg26-catalyzed reaction heavily favors the DHHA intermediate. The high-titer production of the HA product by S. hygroscopicus must be dependent upon a subsequent energetically favorable enzyme-catalyzed process, such as the selective and efficient export of HA. hyg19 encodes a putative proton gradient-dependent transporter, and a mutant lacking this gene was observed to produce less HA and to produce the DHHA intermediate. The DHHA produced by either the Δhyg19 or the Δhyg26 mutant had slightly reduced activity against E. coli and reduced protein synthesis-inhibitory activity in vitro. The data indicate that Hyg26 and Hyg19 have evolved to produce and export the final potent HA product in a coordinated fashion.

scholarly journals Acquisition of Avian Pathogenic Escherichia coli Plasmids by a Commensal E. coli Isolate Enhances Its Abilities To Kill Chicken Embryos, Grow in Human Urine, and Colonize the Murine Kidney

2006 ◽  
Vol 74 (11) ◽  
pp. 6287-6292 ◽  
Author(s):  
Jerod A. Skyberg ◽  
Timothy J. Johnson ◽  
James R. Johnson ◽  
Connie Clabots ◽  
Catherine M. Logue ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Human Urine ◽  
Recipient Strain ◽  
Donor Strain ◽  
Avian Pathogenic Escherichia Coli ◽  
Upec Strain ◽  
Chicken Embryos ◽  
E Coli ◽  
Pathogenic Escherichia Coli

ABSTRACT We have found an avian pathogenic Escherichia coli (APEC) plasmid, pAPEC-O2-ColV, which contains many of the genes associated with APEC virulence and also shows similarity in content to a plasmid and pathogenicity island of human uropathogenic E. coli (UPEC). To test the possible role of this plasmid in virulence, it was transferred by conjugation along with a large R plasmid, pAPEC-O2-R, into a commensal avian E. coli strain. The transconjugant was compared to recipient strain NC, UPEC strain HE300, and donor strain APEC O2 using various assays, including lethality for chicken embryos, growth in human urine, and ability to cause urinary tract infection in mice. The transconjugant killed significantly more chicken embryos than did the recipient. In human urine, APEC O2 grew at a rate equivalent to that of UPEC strain HE300, and the transconjugant showed significantly increased growth compared to the recipient. The transconjugant also significantly outcompeted the recipient in colonization of the murine kidney. These findings suggest that APEC plasmids, such as pAPEC-O2-ColV, contribute to the pathogenesis of avian colibacillosis. Moreover, since avian E. coli and their plasmids may be transmitted to humans, evaluation of APEC plasmids as possible reservoirs of urovirulence genes for human UPEC may be warranted.

Sign in / Sign up

Export Citation Format

Share Document