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Tanabe T, Tsukamoto M, Shioda M, Nagaoka K, Funahashi T. Expression regulation of type III secretion system 2 in Vibrio parahaemolyticus by catabolite activator protein. FEMS Microbiol Lett 2024; 371:fnae054. [PMID: 39054297 DOI: 10.1093/femsle/fnae054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Revised: 06/23/2024] [Accepted: 07/24/2024] [Indexed: 07/27/2024] Open
Abstract
Vibrio parahaemolyticus has two sets of type III secretion systems that are major pathogenic factors: T3SS1 (cytotoxicity) and T3SS2 (enterotoxicity). V. parahaemolyticus mainly colonizes the distal small intestine after oral infection and may be exposed to carbon-limiting stress due to the lack of readily available carbohydrates in this environment. Catabolite activator protein (CAP), a transcription factor involved in carbon-limiting metabolism in many Gram-negative bacteria, is well known to be involved in the regulation of the expression of many virulence factors. In this study, we determined the effects of CAP on the expression of T3SSs in this bacterium. Based on a lactate dehydrogenase-based cytotoxicity assay, CAP was found to have a greater contribution to the expression of T3SS2-dependent cytotoxicity than to that of T3SS1. Reverse transcription quantitative PCR revealed decreased expression of many T3SS2-related genes, including vpa1348, in the cap gene deletion mutant compared to the parent strain. CAP was demonstrated to bind near the T-rich elements within the vpa1348 promoter region in an electrophoretic mobility shift assay and DNase I footprinting. CAP also enhanced the expression of vpa1348 in a β-galactosidase reporter assay. Collectively, these results suggest that CAP is involved in T3SS2-mediated virulence by regulating the expression of vpa1348 in V. parahaemolyticus.
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Affiliation(s)
- Tomotaka Tanabe
- Laboratory of Hygienic Chemistry, College of Pharmaceutical Sciences, Matsuyama University, Matsuyama, Ehime 790-8578, Japan
| | - Mitsuki Tsukamoto
- Laboratory of Hygienic Chemistry, College of Pharmaceutical Sciences, Matsuyama University, Matsuyama, Ehime 790-8578, Japan
| | - Mahiro Shioda
- Laboratory of Hygienic Chemistry, College of Pharmaceutical Sciences, Matsuyama University, Matsuyama, Ehime 790-8578, Japan
| | - Kenjiro Nagaoka
- Laboratory of Hygienic Chemistry, College of Pharmaceutical Sciences, Matsuyama University, Matsuyama, Ehime 790-8578, Japan
| | - Tatsuya Funahashi
- Laboratory of Hygienic Chemistry, College of Pharmaceutical Sciences, Matsuyama University, Matsuyama, Ehime 790-8578, Japan
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Hong SM, Baek DH. A Review of Colonoscopy in Intestinal Diseases. Diagnostics (Basel) 2023; 13:diagnostics13071262. [PMID: 37046479 PMCID: PMC10093393 DOI: 10.3390/diagnostics13071262] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 03/25/2023] [Accepted: 03/26/2023] [Indexed: 03/30/2023] Open
Abstract
Since the development of the fiberoptic colonoscope in the late 1960s, colonoscopy has been a useful tool to diagnose and treat various intestinal diseases. This article reviews the clinical use of colonoscopy for various intestinal diseases based on present and future perspectives. Intestinal diseases include infectious diseases, inflammatory bowel disease (IBD), neoplasms, functional bowel disorders, and others. In cases of infectious diseases, colonoscopy is helpful in making the differential diagnosis, revealing endoscopic gross findings, and obtaining the specimens for pathology. Additionally, colonoscopy provides clues for distinguishing between infectious disease and IBD, and aids in the post-treatment monitoring of IBD. Colonoscopy is essential for the diagnosis of neoplasms that are diagnosed through only pathological confirmation. At present, malignant tumors are commonly being treated using endoscopy because of the advancement of endoscopic resection procedures. Moreover, the characteristics of tumors can be described in more detail by image-enhanced endoscopy and magnifying endoscopy. Colonoscopy can be helpful for the endoscopic decompression of colonic volvulus in large bowel obstruction, balloon dilatation as a treatment for benign stricture, and colon stenting as a treatment for malignant obstruction. In the diagnosis of functional bowel disorder, colonoscopy is used to investigate other organic causes of the symptom.
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Melchior K, Salgaço MK, Sivieri K, Moreira CG. QseC sensor kinase modulates the human microbiota during enterohemorrhagic Escherichia coli O157:H7 infection in the Simulator of the Human Intestinal Microbial Ecosystem (SHIME®). Braz J Microbiol 2023; 54:1-14. [PMID: 36469301 PMCID: PMC9943815 DOI: 10.1007/s42770-022-00877-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Accepted: 11/08/2022] [Indexed: 12/11/2022] Open
Abstract
Enterohemorrhagic Escherichia coli (EHEC) is an important gastrointestinal pathogen known for its ability to cause hemorrhagic colitis and induce hemolytic-uremic syndrome. The inner membrane QseC histidine kinase sensor has shown to be an important regulator of the locus of enterocyte effacement (LEE) island, where important EHEC key virulence genes are located. However, the QseC role during EHEC infection in human microbiota remains unknown. Herein, using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME®), we investigated whether the QseC sensor has a role in human microbiota modulation by EHEC in a dynamic model. Our data demonstrated that the QseC sensor modulates human microbiota during EHEC infection, and its absence leads to an increase in Lactobacillaceae and Bifidobacterium genus predominance, although non-effect on Bacteroides genus by EHEC strains was observed. In co-culture, the Lactobacillus acidophilus has affected EHEC growth and impaired the EHEC growth under space-niche competition, although no growth difference was observed in the QseC sensor presence. Also, differences in EHEC growth were not detected in competition with Bacteroides thetaiotaomicron and EHEC strains did not affect B. thetaiotaomicron growth either. When investigating the mechanisms behind the SHIME results, we found that hcp-2 expression for the type 6 secretion system, known to be involved in bacterial competition, is under QseC sensor regulation beneath different environmental signals, such as glucose and butyrate. Our findings broaden the knowledge about the QseC sensor in modulating the human microbiota and its importance for EHEC pathogenesis.
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Affiliation(s)
- Karine Melchior
- Department of Biological Sciences, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, Brazil
| | - Mateus Kawata Salgaço
- Department of Food and Nutrition, School of Pharmaceutical Sciences, State University of São Paulo (UNESP), Araraquara, SP, Brazil
| | - Katia Sivieri
- Department of Food and Nutrition, School of Pharmaceutical Sciences, State University of São Paulo (UNESP), Araraquara, SP, Brazil
| | - Cristiano Gallina Moreira
- Department of Biological Sciences, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, Brazil.
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Warr AR, Kuehl CJ, Waldor MK. Shiga toxin remodels the intestinal epithelial transcriptional response to Enterohemorrhagic Escherichia coli. PLoS Pathog 2021; 17:e1009290. [PMID: 33529199 PMCID: PMC7880444 DOI: 10.1371/journal.ppat.1009290] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Revised: 02/12/2021] [Accepted: 01/07/2021] [Indexed: 12/22/2022] Open
Abstract
Enterohemorrhagic Escherichia coli (EHEC) is a food-borne pathogen that causes diarrheal disease and the potentially lethal hemolytic uremic syndrome. We used an infant rabbit model of EHEC infection that recapitulates many aspects of human intestinal disease to comprehensively assess colonic transcriptional responses to this pathogen. Cellular compartment-specific RNA-sequencing of intestinal tissue from animals infected with EHEC strains containing or lacking Shiga toxins (Stx) revealed that EHEC infection elicits a robust response that is dramatically shaped by Stx, particularly in epithelial cells. Many of the differences in the transcriptional responses elicited by these strains were in genes involved in immune signaling pathways, such as IL23A, and coagulation, including F3, the gene encoding Tissue Factor. RNA FISH confirmed that these elevated transcripts were found almost exclusively in epithelial cells. Collectively, these findings suggest that Stx potently remodels the host innate immune response to EHEC. Enterohemorrhagic Escherichia coli (EHEC) is a potentially lethal foodborne pathogen. During infection, EHEC releases a potent toxin, Shiga toxin (Stx), into the intestine, but there is limited knowledge of how this toxin shapes the host response to infection. We used an infant rabbit model of infection that closely mimics human disease to profile intestinal transcriptomic responses to EHEC infection. Comparisons of the transcriptional responses to infection by strains containing or lacking Stx revealed that this toxin markedly remodels how the epithelial cell compartment responds to infection. Our findings suggest that Stx shapes the intestinal innate immune response to EHEC and provide insight into the complex host-pathogen dialogue that underlies disease.
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Affiliation(s)
- Alyson R. Warr
- Division of Infectious Diseases, Brigham & Women’s Hospital, Boston, Massachusetts, United States of America
- Department of Microbiology, Harvard Medical School, Boston, Massachusetts, United States of America
| | - Carole J. Kuehl
- Division of Infectious Diseases, Brigham & Women’s Hospital, Boston, Massachusetts, United States of America
- Department of Microbiology, Harvard Medical School, Boston, Massachusetts, United States of America
| | - Matthew K. Waldor
- Division of Infectious Diseases, Brigham & Women’s Hospital, Boston, Massachusetts, United States of America
- Department of Microbiology, Harvard Medical School, Boston, Massachusetts, United States of America
- Howard Hughes Medical Institute, Boston, Massachusetts, United States of America
- * E-mail:
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Tovaglieri A, Sontheimer-Phelps A, Geirnaert A, Prantil-Baun R, Camacho DM, Chou DB, Jalili-Firoozinezhad S, de Wouters T, Kasendra M, Super M, Cartwright MJ, Richmond CA, Breault DT, Lacroix C, Ingber DE. Species-specific enhancement of enterohemorrhagic E. coli pathogenesis mediated by microbiome metabolites. MICROBIOME 2019; 7:43. [PMID: 30890187 PMCID: PMC6425591 DOI: 10.1186/s40168-019-0650-5] [Citation(s) in RCA: 99] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/25/2018] [Accepted: 02/21/2019] [Indexed: 05/24/2023]
Abstract
BACKGROUND Species-specific differences in tolerance to infection are exemplified by the high susceptibility of humans to enterohemorrhagic Escherichia coli (EHEC) infection, whereas mice are relatively resistant to this pathogen. This intrinsic species-specific difference in EHEC infection limits the translation of murine research to human. Furthermore, studying the mechanisms underlying this differential susceptibility is a difficult problem due to complex in vivo interactions between the host, pathogen, and disparate commensal microbial communities. RESULTS We utilize organ-on-a-chip (Organ Chip) microfluidic culture technology to model damage of the human colonic epithelium induced by EHEC infection, and show that epithelial injury is greater when exposed to metabolites derived from the human gut microbiome compared to mouse. Using a multi-omics approach, we discovered four human microbiome metabolites-4-methyl benzoic acid, 3,4-dimethylbenzoic acid, hexanoic acid, and heptanoic acid-that are sufficient to mediate this effect. The active human microbiome metabolites preferentially induce expression of flagellin, a bacterial protein associated with motility of EHEC and increased epithelial injury. Thus, the decreased tolerance to infection observed in humans versus other species may be due in part to the presence of compounds produced by the human intestinal microbiome that actively promote bacterial pathogenicity. CONCLUSION Organ-on-chip technology allowed the identification of specific human microbiome metabolites modulating EHEC pathogenesis. These identified metabolites are sufficient to increase susceptibility to EHEC in our human Colon Chip model and they contribute to species-specific tolerance. This work suggests that higher concentrations of these metabolites could be the reason for higher susceptibility to EHEC infection in certain human populations, such as children. Furthermore, this research lays the foundation for therapeutic-modulation of microbe products in order to prevent and treat human bacterial infection.
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Affiliation(s)
- Alessio Tovaglieri
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA
- Department of Health Sciences and Technology, ETH Zurich, 8092, Zurich, Switzerland
| | - Alexandra Sontheimer-Phelps
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA
- Department of Biology, University of Freiburg, 79085, Freiburg, Germany
| | - Annelies Geirnaert
- Department of Health Sciences and Technology, ETH Zurich, 8092, Zurich, Switzerland
| | - Rachelle Prantil-Baun
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA
| | - Diogo M Camacho
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA
| | - David B Chou
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA
- Department of Pathology, Massachusetts General Hospital, Boston, MA, 02115, USA
| | - Sasan Jalili-Firoozinezhad
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA
- Department of Bioengineering and iBB, Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, 1649-004, Lisbon, Portugal
| | - Tomás de Wouters
- Department of Health Sciences and Technology, ETH Zurich, 8092, Zurich, Switzerland
| | - Magdalena Kasendra
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA
- Present Address: Emulate Inc., 27 Drydock Avenue, Boston, MA, 02210, USA
| | - Michael Super
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA
| | - Mark J Cartwright
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA
| | - Camilla A Richmond
- Division of Gastroenterology, Boston Children's Hospital, Boston, MA, 02115, USA
- Department of Pediatrics, Harvard Medical School, Boston, MA, 02115, USA
- Harvard Stem Cell Institute, Harvard University, Boston, MA, 02139, USA
| | - David T Breault
- Department of Pediatrics, Harvard Medical School, Boston, MA, 02115, USA
- Harvard Stem Cell Institute, Harvard University, Boston, MA, 02139, USA
- Division of Endocrinology, Boston Children's Hospital, Boston, MA, 02115, USA
| | - Christophe Lacroix
- Department of Health Sciences and Technology, ETH Zurich, 8092, Zurich, Switzerland
| | - Donald E Ingber
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA.
- Vascular Biology Program and Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
- Harvard John A. Paulson School of Engineering and Applied Sciences, Cambridge, MA, 02139, USA.
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Antaki-Zukoski EM, Li X, Pesavento PA, Nguyen THB, Hoar BR, Atwill ER. Comparative Pathogenicity of Wildlife and Bovine Escherichia coli O157:H7 Strains in Experimentally Inoculated Neonatal Jersey Calves. Vet Sci 2018; 5:E88. [PMID: 30326606 PMCID: PMC6313898 DOI: 10.3390/vetsci5040088] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2018] [Revised: 10/11/2018] [Accepted: 10/12/2018] [Indexed: 11/23/2022] Open
Abstract
Shiga toxin-producing Escherichia coli, like E. coli O157:H7, are important human and animal pathogens. Naturally-acquired E. coli O157:H7 infections occur in numerous species but, particularly, cattle have been identified as a significant reservoir for human cases. E. coli O157:H7 are isolated from a number of domestic and wild animals, including rodents that share a living space with cattle. These Shiga toxin-producing E. coli O157:H7 strains can be highly virulent in humans, but little is known about the sequelae of interspecies transfer. In a group of neonatal calves, we determined the differences in colonization patterns and lesions associated with infection using either a wildlife or bovine E. coli O157:H7 strain. In calves challenged with the wildlife E. coli O157:H7 strain, the large (descending) colon was solely colonized, which differed substantially from the calves inoculated with the bovine E. coli O157:H7 strain, where the spiral colon was the principal target of infection. This study also demonstrated that while both interspecies- and intraspecies-derived E. coli O157:H7 can infect young calves, the distribution and severity differs.
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Affiliation(s)
- Elizabeth M Antaki-Zukoski
- Department of Population Health and Reproduction, University of California, Davis, CA 95616, USA.
- Western Institute for Food Safety and Security, University of California, Davis, CA 95618, USA.
| | - Xunde Li
- Department of Population Health and Reproduction, University of California, Davis, CA 95616, USA.
- Western Institute for Food Safety and Security, University of California, Davis, CA 95618, USA.
| | - Patricia A Pesavento
- Department of Pathology, Microbiology, and Immunology, University of California, Davis, CA 95616, USA.
| | - Tran H B Nguyen
- Department of Population Health and Reproduction, University of California, Davis, CA 95616, USA.
| | - Bruce R Hoar
- College of Agriculture and Natural Resources, University of Wyoming, Laramie, WY 82071, USA.
| | - Edward R Atwill
- Department of Population Health and Reproduction, University of California, Davis, CA 95616, USA.
- Western Institute for Food Safety and Security, University of California, Davis, CA 95618, USA.
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Zebrafish ( Danio rerio) as a Vertebrate Model Host To Study Colonization, Pathogenesis, and Transmission of Foodborne Escherichia coli O157. mSphere 2017; 2:mSphere00365-17. [PMID: 28959735 PMCID: PMC5607324 DOI: 10.1128/mspheredirect.00365-17] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Accepted: 09/05/2017] [Indexed: 12/12/2022] Open
Abstract
Foodborne infections with enterohemorrhagic Escherichia coli (EHEC) are a major cause of diarrheal illness in humans and can lead to severe complications such as hemolytic uremic syndrome. Cattle and other ruminants are the main reservoir of EHEC, which enters the food chain through contaminated meat, dairy, or vegetables. Here, we describe the establishment of a vertebrate model for foodborne EHEC infection, using larval zebrafish (Danio rerio) as a host and the protozoan prey Paramecium caudatum as a vehicle. We follow pathogen release from the vehicle, intestinal colonization, microbe-host interactions, and microbial gene induction within a live vertebrate host, in real time, throughout the course of infection. We demonstrate that foodborne EHEC colonizes the gastrointestinal tract faster and establishes a higher burden than waterborne infection. Expression of the locus of enterocyte effacement (LEE), a key EHEC virulence factor, was observed early during infection, mainly at sites that experience fluid shear, and required tight control to enable successful host colonization. EHEC infection led to strain- and LEE-dependent mortality in the zebrafish host. Despite the presence of the endogenous microbiota limiting EHEC colonization levels, EHEC colonization and virulence can be studied either under gnotobiotic conditions or against the backdrop of an endogenous (and variable) host microbiota. Finally, we show that the model can be used for investigation of factors affecting shedding and transmission of bacteria to naive hosts. Overall, this constitutes a useful model, which ideally complements the strengths of existing EHEC vertebrate models. IMPORTANCE Enterohemorrhagic Escherichia coli (EHEC) is a foodborne pathogen which can cause diarrhea, vomiting, and, in some cases, severe complications such as kidney failure in humans. Up to 30% of cattle are colonized with EHEC, which can enter the food chain through contaminated meat, dairy, and vegetables. In order to control infections and stop transmission, it is important to understand what factors allow EHEC to colonize its hosts, cause virulence, and aid transmission. Since this cannot be systematically studied in humans, it is important to develop animal models of infection and transmission. We developed a model which allows us to study foodborne infection in zebrafish, a vertebrate host that is transparent and genetically tractable. Our results show that foodborne infection is more efficient than waterborne infection and that the locus of enterocyte effacement is a key virulence determinant in the zebrafish model. It is induced early during infection, and loss of tight LEE regulation leads to a decreased bacterial burden and decreased host mortality. Overall, the zebrafish model allows us to study foodborne infection, including pathogen release from the food vehicle and gene regulation and its context of host-microbe interactions, as well as environmental shedding and transmission to naive hosts.
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Toshniwal J, Chawlani R, Thawrani A, Sharma R, Arora A, Kotecha HL, Goyal M, Kirnake V, Jain P, Tyagi P, Bansal N, Sachdeva M, Ranjan P, Kumar M, Sharma P, Singla V, Bansal R, Shah V, Bhalla S, Kumar A. All ileo-cecal ulcers are not Crohn’s: Changing perspectives of symptomatic ileocecal ulcers. World J Gastrointest Endosc 2017; 9:327-333. [PMID: 28744345 PMCID: PMC5507824 DOI: 10.4253/wjge.v9.i7.327] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2017] [Revised: 05/06/2017] [Accepted: 06/07/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigated clinical, endoscopic and histopathological parameters of the patients presenting with ileocecal ulcers on colonoscopy.
METHODS Consecutive symptomatic patients undergoing colonoscopy, and diagnosed to have ulcerations in the ileocecal (I/C) region, were enrolled. Biopsy was obtained and their clinical presentation and outcome were recorded.
RESULTS Out of 1632 colonoscopies, 104 patients had ulcerations in the I/C region and were included in the study. Their median age was 44.5 years and 59% were males. The predominant presentation was lower GI bleed (55, 53%), pain abdomen ± diarrhea (36, 35%), fever (32, 31%), and diarrhea alone (9, 9%). On colonoscopy, terminal ileum was entered in 96 (92%) cases. The distribution of ulcers was as follows: Ileum alone 40% (38/96), cecum alone 33% (32/96), and both ileum plus cecum 27% (26/96). The ulcers were multiple in 98% and in 34% there were additional ulcers elsewhere in colon. Based on clinical presentation and investigations, the etiology of ulcers was classified into infective causes (43%) and non-infective causes (57%). Fourteen patients (13%) were diagnosed to have Crohn’s disease (CD).
CONCLUSION Non-specific ileocecal ulcers are most common ulcers seen in ileo-cecal region. And if all infections are clubbed together then infection is the most common (> 40%) cause of ulcerations of the I/C region. Cecal involvement and fever are important clues to infective cause. On the contrary CD account for only 13% cases as a cause of ileo-cecalulcers. So all symptomatic patients with I/C ulcers on colonoscopy are not Crohn’s.
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Abstract
The first major outbreaks caused by enterohemorrhagic Escherichia coli (EHEC) raised public and medical awareness of the risks associated with acquiring this potentially deadly infection. The widespread presence of these organisms in the environment, the severity of the clinical sequelae, and the lack of treatment options and effective preventive measures demand that we obtain a better understanding of how this group of organisms cause disease. Animal models allow study of the processes and factors that contribute to disease and, as such, form a valuable tool in the repertoire of infectious disease researchers. Yet despite more than 30 years of research, it seems that no single model host reproduces the full spectrum of clinical disease induced by EHEC in humans. In the first part of this review, a synopsis of what is known about EHEC infections is garnered from human outbreaks and biopsy specimens. The main features and limitations of EHEC infection models that are based on the three most commonly used species (pigs, rabbits, and mice) are described within a historical context. Recent advances are highlighted, and a brief overview of models based on other species is given. Finally, the impact of the host on moderating EHEC infection is considered in light of growing evidence for the need to consider the biology and virulence strategies of EHEC in the context of its niche within the intestine.
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Thévenot J, Cordonnier C, Rougeron A, Le Goff O, Nguyen HTT, Denis S, Alric M, Livrelli V, Blanquet-Diot S. Enterohemorrhagic Escherichia coli infection has donor-dependent effect on human gut microbiota and may be antagonized by probiotic yeast during interaction with Peyer's patches. Appl Microbiol Biotechnol 2015; 99:9097-110. [PMID: 26084888 DOI: 10.1007/s00253-015-6704-0] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2015] [Revised: 05/13/2015] [Accepted: 05/17/2015] [Indexed: 01/05/2023]
Abstract
Enterohemorrhagic Escherichia coli (EHEC) are major food-borne pathogens responsible for serious infections ranging from mild diarrhea to hemorrhagic colitis and life-threatening complications. Shiga toxins (Stxs) are the main virulence factor of EHEC. The antagonistic effect of a prophylactic treatment with the probiotic strain Saccharomyces cerevisiae against EHEC O157:H7 was investigated using complementary in vitro human colonic model and in vivo murine ileal loop assays. In vitro, the probiotic treatment had no effect on O157:H7 survival but favorably influenced gut microbiota activity through modulation of short-chain fatty acid production, increasing acetate production and decreasing that of butyrate. Both pathogen and probiotic strains had individual-dependent effects on human gut microbiota. For the first time, stx expression was followed in human colonic environment: at 9 and 12 h post EHEC infection, probiotic treatment significantly decreased stx mRNA levels. Besides, in murine ileal loops, the probiotic yeast specifically exerted a trophic effect on intestinal mucosa and inhibited O157:H7 interactions with Peyer's patches and subsequent hemorrhagic lesions. Taken together, the results suggest that S. cerevisiae may be useful in the fight against EHEC infection and that host associated factors such as microbiota could influence clinical evolution of EHEC infection and the effectiveness of probiotics.
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Affiliation(s)
- J Thévenot
- Centre de Recherche en Nutrition Humaine Auvergne, EA 4678 CIDAM, Conception Ingénierie et Développement de l'Aliment et du Médicament, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.,Centre de Recherche en Nutrition Humaine Auvergne, M2iSH, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte UMR INSERM / Université d'Auvergne U1071 USC-INRA 2018, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France
| | - C Cordonnier
- Centre de Recherche en Nutrition Humaine Auvergne, EA 4678 CIDAM, Conception Ingénierie et Développement de l'Aliment et du Médicament, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.,Centre de Recherche en Nutrition Humaine Auvergne, M2iSH, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte UMR INSERM / Université d'Auvergne U1071 USC-INRA 2018, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France
| | - A Rougeron
- Centre de Recherche en Nutrition Humaine Auvergne, M2iSH, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte UMR INSERM / Université d'Auvergne U1071 USC-INRA 2018, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France
| | - O Le Goff
- Centre de Recherche en Nutrition Humaine Auvergne, EA 4678 CIDAM, Conception Ingénierie et Développement de l'Aliment et du Médicament, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France
| | - H T T Nguyen
- Centre de Recherche en Nutrition Humaine Auvergne, M2iSH, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte UMR INSERM / Université d'Auvergne U1071 USC-INRA 2018, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France
| | - S Denis
- Centre de Recherche en Nutrition Humaine Auvergne, EA 4678 CIDAM, Conception Ingénierie et Développement de l'Aliment et du Médicament, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France
| | - M Alric
- Centre de Recherche en Nutrition Humaine Auvergne, EA 4678 CIDAM, Conception Ingénierie et Développement de l'Aliment et du Médicament, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France
| | - V Livrelli
- Centre de Recherche en Nutrition Humaine Auvergne, M2iSH, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte UMR INSERM / Université d'Auvergne U1071 USC-INRA 2018, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.,Service de Bactériologie, CHU Clermont-Ferrand, Clermont-Ferrand, France
| | - S Blanquet-Diot
- Centre de Recherche en Nutrition Humaine Auvergne, EA 4678 CIDAM, Conception Ingénierie et Développement de l'Aliment et du Médicament, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.
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Enterohemorrhagic Escherichia coli colonization of human colonic epithelium in vitro and ex vivo. Infect Immun 2014; 83:942-9. [PMID: 25534942 PMCID: PMC4333473 DOI: 10.1128/iai.02928-14] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Enterohemorrhagic Escherichia coli (EHEC) is an important foodborne pathogen causing gastroenteritis and more severe complications, such as hemorrhagic colitis and hemolytic uremic syndrome. Pathology is most pronounced in the colon, but to date there is no direct clinical evidence showing EHEC binding to the colonic epithelium in patients. In this study, we investigated EHEC adherence to the human colon by using in vitro organ culture (IVOC) of colonic biopsy samples and polarized T84 colon carcinoma cells. We show for the first time that EHEC colonizes human colonic biopsy samples by forming typical attaching and effacing (A/E) lesions which are dependent on EHEC type III secretion (T3S) and binding of the outer membrane protein intimin to the translocated intimin receptor (Tir). A/E lesion formation was dependent on oxygen levels and suppressed under oxygen-rich culture conditions routinely used for IVOC. In contrast, EHEC adherence to polarized T84 cells occurred independently of T3S and intimin and did not involve Tir translocation into the host cell membrane. Colonization of neither biopsy samples nor T84 cells was significantly affected by expression of Shiga toxins. Our study suggests that EHEC colonizes and forms stable A/E lesions on the human colon, which are likely to contribute to intestinal pathology during infection. Furthermore, care needs to be taken when using cell culture models, as they might not reflect the in vivo situation.
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Arroyo-López FN, Blanquet-Diot S, Denis S, Thévenot J, Chalancon S, Alric M, Rodríguez-Gómez F, Romero-Gil V, Jiménez-Díaz R, Garrido-Fernández A. Survival of pathogenic and lactobacilli species of fermented olives during simulated human digestion. Front Microbiol 2014; 5:540. [PMID: 25352842 PMCID: PMC4196563 DOI: 10.3389/fmicb.2014.00540] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2014] [Accepted: 09/29/2014] [Indexed: 11/21/2022] Open
Abstract
The present survey uses a dynamic gastric and small intestinal model to assess the survival of one pathogenic (Escherichia coli O157:H7 EDL 933) and three lactobacilli bacteria with probiotic potential (Lactobacillus rhamnosus GG, L. pentosus TOMC-LAB2, and L. pentosus TOMC-LAB4) during their passage through the human gastrointestinal tract using fermented olives as the food matrix. The data showed that the survival of the E. coli strain in the stomach and duodenum was very low, while its transit through the distal parts (jejunum and ileum) resulted in an increase in the pathogen population. The production of Shiga toxins by this enterohemorrhagic microorganism in the ileal effluents of the in vitro system was too low to be detected by ELISA assays. On the contrary, the three lactobacilli species assayed showed a considerable resistance to the gastric digestion, but not to the intestinal one, which affected their survival, and was especially evident in the case of both L. pentosus strains. In spite of this, high population levels for all assayed microorganisms were recovered at the end of the gastrointestinal passage. The results obtained in the present study show the potential use of table olives as a vehicle of beneficial microorganisms to the human body, as well as the need for good hygienic practices on the part of olive manufacturers in order to avoid the possibility of contamination by food-borne pathogens.
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Affiliation(s)
- Francisco N Arroyo-López
- Biotecnología de Alimentos, Instituto de la Grasa - Consejo Superior de Investigaciones Científicas Seville, Spain
| | - Stéphanie Blanquet-Diot
- Centre de Recherche en Nutrition Humaine Auvergne, EA 4678, Conception Ingénierie et Développement de l'Aliment et du Médicament, Clermont Université - Université d'Auvergne Clermont-Ferrand, France
| | - Sylvain Denis
- Centre de Recherche en Nutrition Humaine Auvergne, EA 4678, Conception Ingénierie et Développement de l'Aliment et du Médicament, Clermont Université - Université d'Auvergne Clermont-Ferrand, France
| | - Jonathan Thévenot
- Centre de Recherche en Nutrition Humaine Auvergne, EA 4678, Conception Ingénierie et Développement de l'Aliment et du Médicament, Clermont Université - Université d'Auvergne Clermont-Ferrand, France ; Centre de Recherche en Nutrition Humaine Auvergne, M2iSH, UMR INSERM/Université d'Auvergne U1071 USC-INRA 2018, Clermont Université - Université d'Auvergne Clermont-Ferrand, France
| | - Sandrine Chalancon
- Centre de Recherche en Nutrition Humaine Auvergne, EA 4678, Conception Ingénierie et Développement de l'Aliment et du Médicament, Clermont Université - Université d'Auvergne Clermont-Ferrand, France
| | - Monique Alric
- Centre de Recherche en Nutrition Humaine Auvergne, EA 4678, Conception Ingénierie et Développement de l'Aliment et du Médicament, Clermont Université - Université d'Auvergne Clermont-Ferrand, France
| | - Francisco Rodríguez-Gómez
- Biotecnología de Alimentos, Instituto de la Grasa - Consejo Superior de Investigaciones Científicas Seville, Spain
| | - Verónica Romero-Gil
- Biotecnología de Alimentos, Instituto de la Grasa - Consejo Superior de Investigaciones Científicas Seville, Spain
| | - Rufino Jiménez-Díaz
- Biotecnología de Alimentos, Instituto de la Grasa - Consejo Superior de Investigaciones Científicas Seville, Spain
| | - Antonio Garrido-Fernández
- Biotecnología de Alimentos, Instituto de la Grasa - Consejo Superior de Investigaciones Científicas Seville, Spain
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13
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Zhao L, Hart J. Histologic mimics of inflammatory bowel disease. Semin Diagn Pathol 2014; 31:137-51. [PMID: 24815939 DOI: 10.1053/j.semdp.2014.02.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
This review summarizes a variety of clinical and histologic mimics of idiopathic inflammatory bowel disease. All the entities that are included demonstrate one or more histologic features typical of idiopathic inflammatory bowel disease that may lead to potential diagnostic confusion and misinterpretation by the pathologist. The elements of the clinical history, laboratory test results, and endoscopic findings that are helpful to the surgical pathologist in considering a diagnosis other than idiopathic inflammatory bowel disease are emphasized. On occasion, a poor response to standard treatment for idiopathic inflammatory bowel disease is the clue that prompts reconsideration of the initial diagnosis. Subtle histologic features, special stains, or other diagnostic methodologies that can aid in proper diagnosis are also discussed.
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Affiliation(s)
- Lei Zhao
- Department of Pathology, University of Chicago Medical Center, 5840 S. Maryland Ave., MC6101 Chicago, Illinois 60637
| | - John Hart
- Department of Pathology, University of Chicago Medical Center, 5840 S. Maryland Ave., MC6101 Chicago, Illinois 60637.
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Tadros M, Majumder S, Birk JW. A review of ischemic colitis: is our clinical recognition and management adequate? Expert Rev Gastroenterol Hepatol 2013; 7:605-613. [PMID: 24070152 DOI: 10.1586/17474124.2013.832485] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Ischemic colitis is a common cause of hospital admissions; however it is frequently confused intellectually with mesenteric ischemia and often misdiagnosed as infectious diarrhea or Clostridium difficile colitis. Ischemic colitis is caused by non-occlusive insult to the small vessels supplying the colon without a clear precipitating factor. It is more common in females and in patients above 60 years of age. The classic presentation includes sudden onset of lower abdominal pain followed by the urge to defecate and bloody diarrhea. Focal right-sided ischemic colitis has more pain and a worse prognosis. Choosing the correct diagnostic studies is challenging and requires proficient knowledge of the disease. Management is usually conservative, however around 10-20% of the patients will require surgery. Acute ischemic colitis usually resolves; nevertheless some patients may develop chronic segmental colitis or a stricture. One ischemic colitis caveat is that it may be the first sign of undiagnosed cardiac disease. A firm grasp on this common yet little discussed condition is valuable to a gastrointestinal consultant and hospitalist alike.
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Affiliation(s)
- Michael Tadros
- University of Connecticut Health Center, Division of Gastroenterology & Hepatology, 263 Farmington Avenue, Farmington, USA
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15
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Nagata N, Shimbo T, Sekine K, Tanaka S, Niikura R, Mezaki K, Morino E, Yazaki H, Igari T, Ohmagari N, Akiyama J, Oka S, Uemura N. Combined endoscopy, aspiration, and biopsy analysis for identifying infectious colitis in patients with ileocecal ulcers. Clin Gastroenterol Hepatol 2013; 11:673-80.e2. [PMID: 23357489 DOI: 10.1016/j.cgh.2012.12.034] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2012] [Revised: 12/07/2012] [Accepted: 12/26/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The ileocecal area is commonly involved in infection and inflammatory colonic diseases, but differential diagnosis can be difficult. We identified definitive endoscopic findings and a sample collection method for diagnosing infectious colitis. METHODS In a retrospective study, we analyzed data on 128 patients with ileocecal ulcer who underwent colonoscopy from 2007-2011 at the National Center for Global Health and Medicine in Tokyo, Japan. We collected information on location, size, number, and distinctive endoscopic findings and estimated diagnostic odds ratios (ORs). The sensitivities of microscopy, culture, polymerase chain reaction, and histologic methods in identifying patients with infection were compared with those of standard stool, endoscopic aspirated intestinal fluid, or biopsy analyses. RESULTS Of the 128 patients, 100 had infections, and 28 had Crohn's disease, Behçet's disease, or other inflammatory diseases. Predictive endoscopic findings were as follows: for amebiasis of the cecum (OR, 17.8), with exudates (OR, 13.9) and round-shaped ulcer (OR, 5.77); for tuberculosis (TB) with transverse-shaped ulcer (OR, 175), scar (OR, 34.6), linear-shaped ulcer (OR, 23.9), or ≥10 mm (OR, 14.0); for cytomegalovirus with round-shaped ulcer (OR, 4.09); and for Campylobacter with cecal valve lesion (OR, 58.3) or ≥10 mm (OR, 10.4). The sensitivity of endoscopic sample collection was significantly higher than that of standard stool sample collection for the diagnosis of amebiasis, TB, non-TB mycobacteria, and other bacteria (P < .05). The methods that detected infection with the highest levels of sensitivity were biopsy with histology for amebiasis, biopsy with culture for TB, biopsy with polymerase chain reaction for cytomegalovirus, and aspiration of intestinal fluid with culture for Campylobacter. CONCLUSIONS Combining results from endoscopic analysis with appropriate sample collection and pathogen detection methods enables infectious colitis to be differentiated from other noninfectious colonic diseases.
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Affiliation(s)
- Naoyoshi Nagata
- Department of Gastroenterology and Hepatology, International Clinical Research Center Research Institute, Tokyo, Japan.
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Enterohemorrhagic Escherichia coli O157:H7 survival in an in vitro model of the human large intestine and interactions with probiotic yeasts and resident microbiota. Appl Environ Microbiol 2012. [PMID: 23204410 DOI: 10.1128/aem.03303-12] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
This is the first report on the fate of enterohemorrhagic Escherichia coli O157:H7 in simulated human colonic conditions. The pathogen was progressively eliminated from the bioreactor and did not modify the major populations of resident microbiota. The coadministration of the Saccharomyces cerevisiae CNCM I-3856 probiotic strain led to a significant increase in acetate production but did not reduce pathogen viability.
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17
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Shiga toxin interaction with human intestinal epithelium. Toxins (Basel) 2011; 3:626-39. [PMID: 22069729 PMCID: PMC3202847 DOI: 10.3390/toxins3060626] [Citation(s) in RCA: 86] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2011] [Revised: 06/02/2011] [Accepted: 06/07/2011] [Indexed: 02/03/2023] Open
Abstract
After ingestion via contaminated food or water, enterohaemorrhagic E. coli colonises the intestinal mucosa and produces Shiga toxins (Stx). No Stx-specific secretion system has been described so far, and it is assumed that Stx are released into the gut lumen after bacterial lysis. Human intestinal epithelium does not express the Stx receptor Gb3 or other Stx binding sites, and it remains unknown how Stx cross the intestinal epithelial barrier and gain access to the systemic circulation. This review summarises current knowledge about the influence of the intestinal environment on Stx production and release, Stx interaction with intestinal epithelial cells and intracellular uptake, and toxin translocation into underlying tissues. Furthermore, it highlights gaps in understanding that need to be addressed by future research.
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Abstract
Bacterial colitis results in an inflammatory-type diarrhea that is characterized by bloody, purulent, and mucoid stool. These diseases have been designated as bacterial hemorrhagic enterocolitis. Associated symptoms include fever, tenesmus, and severe abdominal pain. The pathologic changes range from superficial exudative enterocolitis to a transmural enterocolitis with ulceration. Common pathologic bacteria causing bacterial colitis include Campylobacter, Salmonella, Shigella, Escherichia, and Yersinia species. The primary source of transmission is fecal-oral spread and ingestion of contaminated food and water. Although detailed history and identification of specific risk factors assist in the diagnosis, definitive diagnosis requires bacterial identification. Therefore, the physician must be familiar with the disease pathophysiology, epidemiology, and specific diagnostic modalities for clinical diagnosis and management. Specific tests are used to detect enteric pathogens and include stool and rectal swab culture, histology, and identification of specific bacterial toxins. Although many of these bacterial colitis infections are self-limiting, antibiotics should be used for high-risk patients and patients with complicated disease.
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Affiliation(s)
- Harry T Papaconstantinou
- Department of Surgery, Division of Surgical Oncology, Texas A&M University System Health Science Center, Scott and White Hospital, Temple, TX 76508, USA.
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19
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Inoue T, Murano M, Abe Y, Morita E, Murano N, Toshina K, Umegaki E, Hirata I, Higuchi K. Colonoscopic differences of erosive and/or small ulcerative lesions for diagnosis of colonic inflammatory diseases. J Gastroenterol Hepatol 2010; 25 Suppl 1:S149-54. [PMID: 20586858 DOI: 10.1111/j.1440-1746.2010.06233.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIMS Various etiologies and diseases may be related to erosive and/or small ulcerative lesions without gross appearance in the colon during colonoscopy. However, few investigators report on differential diagnosis of colonic inflammatory diseases. Thus, we investigated the clinical significance of these lesions and the value of colonoscopy in the differential diagnosis of colitis. METHODS In 110 patients with erosive and/or small ulcerative lesions (<5 mm) who were treated in our hospital during the past 9 years, we retrospectively investigated the relationship between endoscopic morphology and clinical diagnosis. The intestinal lesions were endoscopically classified into three groups (A, hyperemic type; B, aphthous type; and C, verrucous type). RESULTS The lesions were mainly located in the rectum to the sigmoid colon in group A. In group C, the lesions were most frequently located in the transverse colon and deeper areas. Endoscopically, the etiology was unclear in 74.5% of group A and 73.8% of group B, however, in group C, most of them (81.0%) were associated with specific diseases. With respect to inflammatory bowel diseases, 71.4% of the patients with Crohn's disease and all patients with ulcerative colitis were assigned to group A or B. CONCLUSION Erosive and/or small ulcerative lesions belonging to group A or B were mainly non-specific. However, careful follow up was required in groups A and B, which included the possibility of inflammatory bowel diseases, when the symptoms or lesions were not improved.
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Affiliation(s)
- Takuya Inoue
- Second Department of Internal Medicine, Osaka Medical College, Takatsuki City, Osaka, Japan
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20
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Baines D, Lee B, McAllister T. Heterogeneity in enterohemorrhagicEscherichia coliO157:H7 fecal shedding in cattle is related toEscherichia coliO157:H7 colonization of the small and large intestine. Can J Microbiol 2008; 54:984-95. [DOI: 10.1139/w08-090] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
In the last decade, Escherichia coli O157:H7 have emerged as important pathogens of the gastrointestinal tract of humans. Healthy cattle have been identified as the primary reservoir, however, the factors affecting heterogeneous E. coli O157:H7 fecal shedding are not fully understood. The aim of this study was to investigate the contribution of E. coli O157:H7 colonization of small and large intestinal sites to the heterogeneity of fecal shedding in cattle. There was a dose-dependant E. coli O157:H7 E318N colonization of duodenum, jejunum, ileum, cecum, ascending colon, spiral colon, descending colon, and the rectoanal junction in vitro with no difference in E. coli O157:H7 colonization of the rectoanal junction and other intestinal sites. There were 10–100 times greater E. coli O157:H7 colonization of intestinal sites from persistent shedding cattle compared with nonpersistent shedding cattle. Novel pathologies were associated with E. coli O157:H7 colonization sites in the small and large intestine. The first pathology, focal petechiae, was present throughout the intestinal tract of cattle that ceased shedding E. coli O157:H7 for 5–12 weeks or in the jejunum, ileum, cecum, and ascending colon of cattle shedding E. coli O157:H7 for 4–5 months. The second pathology, mucosal hemorrhages, was present in the same sites as the focal petechiae in cattle shedding for 5 months and these hemorrhages were in the final stages of repair. Several features of these hemorrhages support this conclusion including the brown appearance, low amount of classic E. coli O157:H7 induced A/E lesions, flattened epithelium, and blunted villi. Although mucosal hemorrhages were present in the jejunum, ileum, cecum, and ascending colon in cattle shedding for 4 months, many other pathologies were also present that were indicative of hemorrhagic enteritis as evidenced by the blood red appearance of hemorrhages, severe edema, and dark red erythema. Escherichia coli O157:H7 were associated with both pathologies suggesting it is the causative agent. The current study supports a relationship between the amount of E. coli O157:H7 colonization in intestinal sites and heterogeneous fecal shedding by cattle.
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Affiliation(s)
- Danica Baines
- Lethbridge Research Centre, Agriculture and Agri-Food Canada, Lethbridge, AB T1J 4B1, Canada
| | - Byron Lee
- Lethbridge Research Centre, Agriculture and Agri-Food Canada, Lethbridge, AB T1J 4B1, Canada
| | - Tim McAllister
- Lethbridge Research Centre, Agriculture and Agri-Food Canada, Lethbridge, AB T1J 4B1, Canada
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21
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Clostridium septicum myonecrosis complicating diarrhea-associated hemolytic uremic syndrome. Pediatr Nephrol 2008; 23:1171-5. [PMID: 18301926 DOI: 10.1007/s00467-008-0774-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2007] [Revised: 01/18/2008] [Accepted: 01/22/2008] [Indexed: 10/22/2022]
Abstract
We report the case of a 19-month-old male child with diarrhea-associated hemolytic uremic syndrome (HUS) who developed swelling of the right arm at the site of a peripherally inserted central venous catheter (PICC), fever, and later, ecchymosis. Wound cultures at the time of surgical debridement grew Clostridium septicum. The child subsequently required amputation of the right arm and prolonged therapy with parenteral penicillin and clindamycin. Clostridium septicum infections in children with HUS have been associated with a high rate of mortality. Along with colon cancer, diarrhea-associated HUS comprises a clinical entity which appears to predispose to atraumatic C. septicum infection, where acidic and anaerobic conditions in the diseased colon favor C. septicum invasion. Though not well recognized among pediatric nephrologists, C. septicum infection constitutes a severe, albeit rare, complication of diarrhea-associated HUS, but one in which a high index of suspicion is warranted as aggressive surgical and antibiotic therapy may be life-saving.
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Shigeno T, Akamatsu T, Fujimori K, Nakatsuji Y, Nakamura Y. EVALUATION OF COLONOSCOPIC FINDINGS IN PATIENTS WITH DIARRHEAGENIC ESCHERICHIA COLI-INDUCED HEMORRHAGIC COLITIS. Dig Endosc 2008. [DOI: 10.1111/j.1443-1661.2008.00789.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/23/2023]
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Yoon JW, Lim JY, Park YH, Hovde CJ. Involvement of the Escherichia coli O157:H7(pO157) ecf operon and lipid A myristoyl transferase activity in bacterial survival in the bovine gastrointestinal tract and bacterial persistence in farm water troughs. Infect Immun 2005; 73:2367-78. [PMID: 15784583 PMCID: PMC1087426 DOI: 10.1128/iai.73.4.2367-2378.2005] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Escherichia coli O157:H7 is an important food-borne pathogen that causes hemorrhagic colitis and the hemolytic-uremic syndrome in humans. Recently, we reported that the pO157 ecf (E. coli attaching and effacing gene-positive conserved fragments) operon is thermoregulated by an intrinsically curved DNA and contains the genes for bacterial surface-associated proteins, including a second copy of lipid A myristoyl transferase, whose chromosomal copy is the lpxM gene product. E. coli O157:H7 survives and persists well in diverse environments from the human and bovine gastrointestinal tracts (GIT) to nutrient-dilute farm water troughs. Transcriptional regulation of the ecf operon by intrinsic DNA curvature and the genetic redundancy of lpxM that is associated with lipid A modification led us to hypothesize that the pO157 ecf operon and lpxM are associated with bacterial survival and persistence in various in vivo and ex vivo environments by optimizing bacterial membrane structure and/or integrity. To test this hypothesis, three isogenic ecf operon and/or lpxM deletion mutants of E. coli O157:H7 ATCC 43894 were constructed and analyzed in vitro and in vivo. The results showed that a double mutant carrying deletions in the ecf and lpxM genes had an altered lipid A structure and membrane fatty acid composition, did not survive passage through the bovine GIT, did not persist well in farm water troughs, had increased susceptibility to a broad spectrum of antibiotics and detergents, and had impaired motility. Electron microscopic analyses showed gross changes in bacterial membrane structure.
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Affiliation(s)
- Jang W Yoon
- Department of Microbiology, Molecular Biology and Biochemistry, University of Idaho, Moscow, ID 83844-3052, USA
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24
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Yoon JW, Minnich SA, Ahn JS, Park YH, Paszczynski A, Hovde CJ. Thermoregulation of the Escherichia coli O157:H7 pO157 ecf operon and lipid A myristoyl transferase activity involves intrinsically curved DNA. Mol Microbiol 2004; 51:419-35. [PMID: 14756783 DOI: 10.1046/j.1365-2958.2003.03827.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Escherichia coli O157:H7 survives in diverse environments from the ruminant gastrointestinal tract to cool nutrient-dilute water. We hypothesized that the gene regulation required for this flexibility includes intrinsically curved DNA that responds to environmental changes. Three intrinsically curved DNAs were cloned from the E. coli O157:H7 virulence plasmid (pO157), sequenced and designated Bent 1 through Bent 3 (BNT1, BNT2 and BNT3). Compared to BNT1 and BNT3, BNT2 had characteristics typical of intrinsically curved DNA including electrophoretic gel retardation at 4 degrees C, six partially phased adenine:thymine tracts and transcriptional activation. BNT2::lacZ operon fusions showed that BNT2 activated transcription at 24 degrees C compared to 37 degrees C and was partially repressed by a bacterial nucleoid-associated protein H-NS. BNT2 regulated the E. coli attaching and effacing gene-positive conserved fragments 1-4 (ecf1-4) that are conserved in Shiga toxin-producing E. coli associated with human disease. Experimental analyses showed that ecf1-4 formed an operon. ecf1, 2 and 3 encoded putative proteins associated with bacterial surface polysaccharide biosynthesis and invasion and ecf4 complemented a chromosomal deletion of lpxM encoding lipid A myristoyl transferase. Mass spectrometric analysis of lipid A from ecf and lpxM single and double mutants showed that myristoylation was altered at lower temperature.
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Affiliation(s)
- Jang W Yoon
- Department of Microbiology, Molecular Biology and Biochemistry, University of Idaho, Moscow, ID 83844-3052, USA
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Abstract
PURPOSE OF REVIEW The Shiga toxin-producing Escherichia coli strains, such as E. coli O157:H7, have emerged as major diarrheal pathogens both in the United States and elsewhere. These organisms are important because gastrointestinal infection (afebrile hemorrhagic colitis) can trigger microangiopathic hemolytic anemia and renal failure (hemolytic uremic syndrome). Understanding the pathophysiology of this illness is likely to lead to important new treatment interventions. RECENT FINDINGS It is now recognized that children with hemorrhagic colitis routinely develop a spectrum of coagulation abnormalities and that only a fraction of children develop full blown hemolytic uremic syndrome. Individual variability in expression of inflammatory mediators is likely to be a key element in determining which children progress to the severe end of the spectrum of disease. The value of antibiotic therapy is unknown. SUMMARY The pathophysiology of HUS remains incompletely understood. The lag between onset of diarrhea and onset of HUS represents an opportunity to intervene and prevent renal failure. However, there currently is no way to prevent such life threatening complications. The management should focus on diagnosis and close observation so that early intervention can prevent complications.
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Affiliation(s)
- Theresa J Ochoa
- Department of Pediatrics, University of Texas, Houston Health Science Center, Houston, Texas 77030, USA
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