Shiga toxin 2a and Enteroaggregative Escherichia coli - a deadly combination (original) (raw)
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Enterohemorrhagic Escherichia coli and Other Shiga Toxin-Producing E. coli, 2015
A major outbreak caused by Escherichia coli of serotype O104:H4 spread throughout Europe in 2011. This large outbreak was caused by an unusual strain that is most similar to enteroaggregative E. coli (EAEC) of serotype O104:H4. A significant difference, however, is the presence of a prophage encoding the Shiga toxin, which is characteristic of enterohemorrhagic E. coli (EHEC) strains. This combination of genomic features, associating characteristics from both EAEC and EHEC, represents a new pathotype. The 2011 E. coli O104:H4 outbreak of hemorrhagic diarrhea in Germany is an example of the explosive cocktail of high virulence and resistance that can emerge in this species. A total of 46 deaths, 782 cases of hemolytic-uremic syndrome, and 3,128 cases of acute gastroenteritis were attributed to this new clone of EAEC/EHEC. In addition, recent identification in France of similar O104:H4 clones exhibiting the same virulence factors suggests that the EHEC O104:H4 pathogen has become endemically established in Europe after the end of the outbreak. EAEC strains of serotype O104:H4 contain a large set of virulence-associated genes regulated by the AggR transcription factor. They include, among other factors, the pAA plasmid genes encoding the aggregative adherence fimbriae, which anchor the bacterium to the intestinal mucosa (stacked-brick adherence pattern on epithelial cells). Furthermore, sequencing studies showed that horizontal genetic exchange allowed for the emergence of the highly virulent Shiga toxin-producing EAEC O104:H4 strain that caused the German outbreak. This article discusses the role these virulence factors could have in EAEC/EHEC O104:H4 pathogenesis.
A novel murine infection model for Shiga toxin–producing Escherichia coli
Journal of Clinical Investigation, 2012
Enterohemorrhagic E. coli (EHEC) is an important subset of Shiga toxin-producing (Stx-producing) E. coli (STEC), pathogens that have been implicated in outbreaks of food-borne illness and can cause intestinal and systemic disease, including severe renal damage. Upon attachment to intestinal epithelium, EHEC generates "attaching and effacing" (AE) lesions characterized by intimate attachment and actin rearrangement upon host cell binding. Stx produced in the gut transverses the intestinal epithelium, causing vascular damage that leads to systemic disease. Models of EHEC infection in conventional mice do not manifest key features of disease, such as AE lesions, intestinal damage, and systemic illness. In order to develop an infection model that better reflects the pathogenesis of this subset of STEC, we constructed an Stx-producing strain of Citrobacter rodentium, a murine AE pathogen that otherwise lacks Stx. Mice infected with Stx-producing C. rodentium developed AE lesions on the intestinal epithelium and Stx-dependent intestinal inflammatory damage. Further, the mice experienced lethal infection characterized by histopathological and functional kidney damage. The development of a murine model that encompasses AE lesion formation and Stx-mediated tissue damage will provide a new platform upon which to identify EHEC alterations of host epithelium that contribute to systemic disease.
Infection and Immunity, 2013
ABSTRACTIn May 2011, a large food-borne outbreak was traced to an unusual O104:H4 enteroaggregativeEscherichia coli(EAEC) strain that produced Shiga toxin (Stx) type 2 (Stx2). We developed a mouse model to study the pathogenesis and treatment for this strain and examined the virulence of the isolate for Dutch belted rabbits. O104:H4 strain C227-11 was gavaged into C57BL/6 mice at 109to 1011CFU/animal. The infected animals were then given water with ampicillin (& 5 g/liter)ad libitum. The C227-11-infected, Amp-treated C57BL/6 mice exhibited both morbidity and mortality. Kidneys from mice infected with C227-11 showed acute tubular necrosis, a finding seen in mice infected with typical Stx-producingE. coli. We provided anti-Stx2 antibody after infection and found that all of the antibody-treated mice gained more weight than untreated mice and, in another study, that all of the antibody-treated animals lived, whereas 3/8 phosphate-buffered saline-treated mice died. We further compared t...
International journal of medical microbiology : IJMM, 2018
In February 2017 a case of Hemolytic-Uremic Syndrome (HUS) was reported to the National Registry of HUS in an adult living in Northern Italy. Stool specimens from the patient and his family contacts were collected and the analyses led to the isolation of a Locus of Enterocyte Effacement (LEE)-negative Shiga toxin 2 (Stx2)-producing Escherichia coli. The epidemiological investigations performed brought to collect fecal samples from the animals reared in a farm held by the case's family and a mixture of bovine and swine feces proved positive for Shiga toxin-producing E. coli (STEC) and yielded the isolation of a LEE-negative stx2-positive E. coli strain. Further characterization by whole genome sequencing led to identify the isolates as two identical O2:H27 hybrid Enterotoxigenic Shiga toxin-producing E. coli (ETEC-STEC). Sequencing of a high molecular weight plasmid present in the human isolate disclosed a peculiar plasmid harboring virulence genes characteristic for both pathoty...
Lessons Learned From Outbreaks of Shiga Toxin Producing Escherichia coli
Current Infectious Disease Reports, 2012
In 2011, a large outbreak caused by a Shiga toxin producing E. coli (STEC) occurred in Northern Germany, with a satellite outbreak in Western France, including the highest number of hemolytic uremic syndrome (HUS) cases ever encountered during a STEC outbreak. The outbreak strain was characterized as an enteroaggregative E. coli of serotype O104:H4 expressing a phage-encoded Shiga toxin 2. The majority of STEC infections and HUS cases were observed in adults, with a preponderance of the female gender. The outbreak imposed huge challenges on clinicians, microbiologists, and epidemiologists but also provided important new insight for the understanding of STEC infection. Thus, novel therapeutic strategies in the treatment of HUS in adults and for decolonization of long-term STEC carriers were evaluated. This review highlights the unusual features of the recent O104:H4 outbreak and focuses on emerging new strategies in diagnostics and treatment of acute STEC-related disease, as well as STEC long-term carriage.
The Journal of infectious diseases, 2014
A Shiga toxin type 2a (Stx2a)-producing enteroaggregative Escherichia coli (EAEC) strain of serotype O104:H4 caused a large outbreak in 2011 in northern Europe. Pathogenic mechanisms for this strain are unclear. We hypothesized that EAEC genes encoded on the pAA virulence plasmid promoted the translocation of Stx2a across the intestinal mucosa. We investigated the potential contribution of pAA by using mutants of Stx-EAEC strain C227-11, either cured of the pAA plasmid or deleted for individual known pAA-encoded virulence genes (ie, aggR, aggA, and sepA). The resulting mutants were tested for their ability to induce interleukin 8 (IL-8) secretion and translocation of Stx2a across a polarized colonic epithelial (T84 cell) monolayer. We found that deletion of aggR or aggA significantly reduced bacterial adherence and (independently) translocation of Stx2a across the T84-cell monolayer. Moreover, deletion of aggR, aggA, sepA, or the Stx2a-encoding phage from C227-11 resulted in reduced...
Clinical Infectious Diseases, 2008
Attaching and effacing Escherichia coli (AEEC) that lack Shiga toxin genes (stx) and the enteropathogenic E. coli adherence factor (EAF) plasmid (stx-/EAF-) are classified as atypical enteropathogenic E. coli and cause diarrhea worldwide. However, it is unknown whether there are bacterial lineage-specific human disease phenotypes. We compared stx-/EAF- AEEC recovered from patients (mostly children) with bloody and nonbloody diarrhea. stx-/EAF- AEEC were isolated using eae colony blot hybridization and were serotyped, tested (by polymerase chain reaction) for putative virulence genes, and analyzed for phylogenetic relationships by use of multilocus sequence typing. During the period 1995-2007, stx-/EAF- AEEC were isolated as the only bacterial pathogens from stool specimens obtained from 18 (15.3%) of 118 patients with bloody diarrhea and from 141 (1.3%) of 10,550 patients with nonbloody diarrhea (P<.001). All but 1 of 18 strains recovered from patients with bloody diarrhea resembled enterohemorrhagic E. coli (EHEC) on the basis of serotypes, non-stx virulence profiles, and multilocus sequence types. In contrast, most (75.9%) of 141 stx-/EAF- AEEC recovered from patients with nonbloody diarrhea belonged to other serotypes and differed from the former strains phylogenetically and with regard to virulence genes. Three of 18 patients with bloody diarrhea and none of 141 patients with nonbloody diarrhea who shedded stx-/EAF- AEEC developed hemolytic uremic syndrome. Most stx-/EAF- AEEC associated with bloody diarrhea are plausibly EHEC that lost Shiga toxin during infection (EHEC-LST). To prevent serious complications of such infections, Shiga toxin-independent diagnostic strategies to accurately and rapidly identify such patients should be developed and applied. Multilocus sequence typing has potential to distinguish EHEC-LST from less pathogenic stx-/EAF- AEEC.
Escherichia coli encoding Shiga toxin subtype Stx2f causing human infections in England, 2015–2022
Journal of Medical Microbiology
Introduction. Shiga toxin-producing Escherichia coli (STEC) belong to a diverse group of gastrointestinal pathogens defined by the presence of Shiga toxin genes (stx) of which there are at least ten subtypes (Stx1a-Stx1d and Stx2a-Stx2g). Gap Statement. Initially thought to be associated with mild symptoms, more recently STEC encoding stx2f have been isolated from cases of haemolytic uraemic syndrome (HUS) and the clinical significance and public health burden require further investigation. Aim. We analysed clinical outcomes and genome-sequencing data linked to patients infected with STEC encoding-stx2f in England to assess the risk to public health. Methodology. One hundred and twelve E. coli (n=58 isolates encoded stx2f; n=54 isolates E. coli belonging to CC122 or CC722 that had eae but were negative for stx) isolated from patients' faecal specimens between 2015 and 2022 were genome sequenced and linked to epidemiological and clinical outcome data. All isolates were investigat...