Adherence of Enterohemorrhagic Escherichia coli to Human Epithelial Cells: The Role of Intimin

1995 ◽  
Author(s):  
Marian L McKee
2021 ◽  
Author(s):  
Mihaela Anca Serbanescu

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a gastrointestinal pathogen which causes hemorrhagic colitis and can lead to neurological damage, acute kidney failure (hemolytic uremic syndrome and vascular lesions. During intestinal colonization EHEC is exposed to a variety of stresses including bile salts (BS) in the small intestine and short chain fatty acids (SCFA) in the large intestine; little is known about how these stresses affect this pathogen's virulence properties. The goal of this study was to investigate the impact of exposure of E. coli O157:H7 to physiologically relevant concentrations of BS and SCFA alone and in mixtures on bacterial survival, verotoxin production and adhesion to human epithelial cells. The results indicated that BS treatments significantly enhanced several virulence properties including survival and adhesion to human epthelial cell lines including colonic epithelial cells. Verotoxin production was not affected by any of the BS treatments. Bacterial pretreatment with erythromycin at a sub-minimal inhibitory concentration eliminated the adhesion enhancement after BS treatment, suggesting that protein synthesis was required for enhanced adhesion of BS treated organisms. Using the isogenci mutant of the known adhesions, intimin and iha it was established that there was no role for intimin or iha in the BS-induced adhesion enhancement. SCFA treatments reduced bacterial viability but significantly enhanced both adhesion to human epithelial cells and verotoxin production. The results of this research indicate that ingestion stresses such as BS and SCFA, which are part of the host's natural chemical assault on foreign organisms, may actually enhance the viulence properties of this pathogen and contribute to, rather than, prevent infection. Furthermore, they suggest that this pathogen may use these ingestion stresses to cue the expression of numerous virulence factors for successful infection of local microenvironments.


2021 ◽  
Author(s):  
Mihaela Anca Serbanescu

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a gastrointestinal pathogen which causes hemorrhagic colitis and can lead to neurological damage, acute kidney failure (hemolytic uremic syndrome and vascular lesions. During intestinal colonization EHEC is exposed to a variety of stresses including bile salts (BS) in the small intestine and short chain fatty acids (SCFA) in the large intestine; little is known about how these stresses affect this pathogen's virulence properties. The goal of this study was to investigate the impact of exposure of E. coli O157:H7 to physiologically relevant concentrations of BS and SCFA alone and in mixtures on bacterial survival, verotoxin production and adhesion to human epithelial cells. The results indicated that BS treatments significantly enhanced several virulence properties including survival and adhesion to human epthelial cell lines including colonic epithelial cells. Verotoxin production was not affected by any of the BS treatments. Bacterial pretreatment with erythromycin at a sub-minimal inhibitory concentration eliminated the adhesion enhancement after BS treatment, suggesting that protein synthesis was required for enhanced adhesion of BS treated organisms. Using the isogenci mutant of the known adhesions, intimin and iha it was established that there was no role for intimin or iha in the BS-induced adhesion enhancement. SCFA treatments reduced bacterial viability but significantly enhanced both adhesion to human epithelial cells and verotoxin production. The results of this research indicate that ingestion stresses such as BS and SCFA, which are part of the host's natural chemical assault on foreign organisms, may actually enhance the viulence properties of this pathogen and contribute to, rather than, prevent infection. Furthermore, they suggest that this pathogen may use these ingestion stresses to cue the expression of numerous virulence factors for successful infection of local microenvironments.


2008 ◽  
Vol 88 (1) ◽  
pp. 41-50 ◽  
Author(s):  
Danica Baines ◽  
Luke Masson ◽  
Tim McAllister

Enterohemorrhagic Escherichia coli (EHEC) O157:H7-secreted cytotoxins are toxic to target cells and enhance colonization of intestinal tissues in disease-susceptible animals. It is unclear what role, if any, EHEC O157:H7-secreted cytotoxins play in the colonization of intestinal tissues of healthy reservoir animals. We previously reported that EHEC O157:H7 colonization sites were associated with focal hemorrhages in the jejunum and descending colon of persistent shedding cattle, suggesting a potential role for cytotoxins in EHEC O157:H7 colonization. We have used a traditional EHEC O157:H7 IVOC adherence assay and a novel lawn assay to examine the role of EHEC O157:H7-secreted cytotoxins in EHEC O157:H7 strain colonization of the jejunum and descending colon of non-persistent and persistent shedding cattle. Four EHEC O157:H7 strains that were previously reported to differentially colonize cattle produced cytotoxins that were differentially active against epithelial cells from the jejunum and descending colon. There was a relationship between EHEC O157:H7-secreted cytotoxin activity and strain adherence for epithelial cells from the jejunum and descending colon of cattle. There was also a greater susceptibility of epithelial cells from the jejunum and descending colon to EHEC O157:H7-secreted cytotoxins of persistent shedding cattle compared with non-persistent shedding cattle. Addition of the most active secreted cytotoxins from EHEC O157:H7 R318N to the IVOC adherence assays significantly increased the adhere nce of the most (R318N) and least (H4420N) virulent EHEC O157:H7 strain to intestinal tissues. The current study supports a role for EHEC O157:H7-secreted cytotoxins in enhancing EHEC O157:H7 colonization of intestinal tissues of cattle. Key words: Escherichia coli O157:H7, cattle, intestine, cytotoxins, colonization


1998 ◽  
Vol 188 (10) ◽  
pp. 1907-1916 ◽  
Author(s):  
Akio Abe ◽  
Ursula Heczko ◽  
Richard G. Hegele ◽  
B. Brett Finlay

Enteropathogenic Escherichia coli (EPEC) belongs to a family of related bacterial pathogens, including enterohemorrhagic Escherichia coli (EHEC) O157:H7 and other human and animal diarrheagenic pathogens that form attaching and effacing (A/E) lesions on host epithelial surfaces. Bacterial secreted Esp proteins and a type III secretion system are conserved among these pathogens and trigger host cell signal transduction pathways and cytoskeletal rearrangements, and mediate intimate bacterial adherence to epithelial cell surfaces in vitro. However, their role in pathogenesis is still unclear. To investigate the role of Esp proteins in disease, mutations in espA and espB were constructed in rabbit EPEC serotype O103 and infection characteristics were compared to that of the wild-type strain using histology, scanning and transmission electron microscopy, and confocal laser scanning microscopy in a weaned rabbit infection model. The virulence of EspA and EspB mutant strains was severely attenuated. Additionally, neither mutant strain formed A/E lesions, nor did either one cause cytoskeletal actin rearrangements beneath the attached bacteria in the rabbit intestine. Collectively, this study shows for the first time that the type III secreted proteins EspA and EspB are needed to form A/E lesions in vivo and are indeed virulence factors. It also confirms the role of A/E lesions in disease processes.


mBio ◽  
2015 ◽  
Vol 6 (2) ◽  
Author(s):  
Amin Zargar ◽  
David N. Quan ◽  
Karen K. Carter ◽  
Min Guo ◽  
Herman O. Sintim ◽  
...  

ABSTRACTThere have been many studies on the relationship between nonpathogenic bacteria and human epithelial cells; however, the bidirectional effects of the secretomes (secreted substances in which there is no direct bacterium-cell contact) have yet to be fully investigated. In this study, we use a transwell model to explore the transcriptomic effects of bacterial secretions from two different nonpathogenicEscherichia colistrains on the human colonic cell line HCT-8 using next-generation transcriptome sequencing (RNA-Seq).E. coliBL21 and W3110, while genetically very similar (99.1% homology), exhibit key phenotypic differences, including differences in their production of macromolecular structures (e.g., flagella and lipopolysaccharide) and in their secretion of metabolic byproducts (e.g., acetate) and signaling molecules (e.g., quorum-sensing autoinducer 2 [AI-2]). After analysis of differential epithelial responses to the respective secretomes, this study shows for the first time that a nonpathogenic bacterial secretome activates the NF-κB-mediated cytokine-cytokine receptor pathways while also upregulating negative-feedback components, including the NOD-like signaling pathway. Because of AI-2's relevance as a bacterium-bacterium signaling molecule and the differences in its secretion rates between these strains, we investigated its role in HCT-8 cells. We found that the expression of the inflammatory cytokine interleukin 8 (IL-8) responded to AI-2 with a pattern of rapid upregulation before subsequent downregulation after 24 h. Collectively, these data demonstrate that secreted products from nonpathogenic bacteria stimulate the transcription of immune-related biological pathways, followed by the upregulation of negative-feedback elements that may serve to temper the inflammatory response.IMPORTANCEThe symbiotic relationship between the microbiome and the host is important in the maintenance of human health. There is a growing need to further understand the nature of these relationships to aid in the development of homeostatic probiotics and also in the design of novel antimicrobial therapeutics. To our knowledge, this is the first global-transcriptome study of bacteria cocultured with human epithelial cells in a model to determine the transcriptional effects of epithelial cells in which epithelial and bacterial cells are allowed to “communicate” with each other only through diffusible small molecules and proteins. By beginning to demarcate the direct and indirect effects of bacteria on the gastrointestinal (GI) tract, two-way interkingdom communication can potentially be mediated between host and microbe.


2015 ◽  
Vol 148 (4) ◽  
pp. S-10
Author(s):  
Charlotte Cordonnier ◽  
Jonathan Thévenot ◽  
Lucie Etienne-Mesmin ◽  
Amandine Rougeron ◽  
Sandra Renier ◽  
...  

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