scholarly journals Mouse Models ofEscherichia coliO157:H7 Infection and Shiga Toxin Injection

2011 ◽  
Vol 2011 ◽  
pp. 1-17 ◽  
Author(s):  
Krystle L. Mohawk ◽  
Alison D. O'Brien

Escherichia coliO157:H7 has been responsible for multiple food- and waterborne outbreaks of diarrhea and/or hemorrhagic colitis (HC) worldwide. More importantly, a portion ofE. coliO157:H7-infected individuals, particularly young children, develop a life-threatening sequela of infection called hemolytic uremic syndrome (HUS). Shiga toxin (Stx), a potent cytotoxin, is the major virulence factor linked to the presentation of both HC and HUS. Currently, treatment ofE. coliO157:H7 and other Stx-producingE. coli(STEC) infections is limited to supportive care. To facilitate development of therapeutic strategies and vaccines for humans against these agents, animal models that mimic one or more aspect of STEC infection and disease are needed. In this paper, we focus on the characteristics of various mouse models that have been developed and that can be used to monitor STEC colonization, disease, pathology, or combinations of these features as well as the impact of Stx alone.

2020 ◽  
Vol 86 (9) ◽  
Author(s):  
Yibao Chen ◽  
Xiangmin Li ◽  
Shuang Wang ◽  
Lingyu Guan ◽  
Xinxin Li ◽  
...  

ABSTRACT Shiga toxin-producing Escherichia coli (STEC) strains are important zoonotic foodborne pathogens, causing diarrhea, hemorrhagic colitis, and life-threatening hemolytic uremic syndrome (HUS) in humans. However, antibiotic treatment of STEC infection is associated with an increased risk of HUS. Therefore, there is an urgent need for early and effective therapeutic strategies. Here, we isolated lytic T7-like STEC phage PHB19 and identified a novel O91-specific polysaccharide depolymerase (Dep6) in the C terminus of the PHB19 tailspike protein. Dep6 exhibited strong hydrolase activity across wide ranges of pH (pH 4 to 8) and temperature (20 to 60°C) and degraded polysaccharides on the surface of STEC strain HB10. In addition, both Dep6 and PHB19 degraded biofilms formed by STEC strain HB10. In a mouse STEC infection model, delayed Dep6 treatment (3 h postinfection) resulted in only 33% survival, compared with 83% survival when mice were treated simultaneously with infection. In comparison, pretreatment with Dep6 led to 100% survival compared with that of the control group. Surprisingly, a single PHB19 treatment resulted in 100% survival in all three treatment protocols. Moreover, a significant reduction in the levels of proinflammatory cytokines was observed at 24 h postinfection in Dep6- or PHB19-treated mice. These results demonstrated that Dep6 or PHB19 might be used as a potential therapeutic agent to prevent STEC infection. IMPORTANCE Shiga toxin-producing Escherichia coli (STEC) is an important foodborne pathogen worldwide. The Shiga-like toxin causes diarrhea, hemorrhagic colitis, and life-threatening hemolytic uremic syndrome (HUS) in humans. Although antibiotic therapy is still used for STEC infections, this approach may increase the risk of HUS. Phages or phage-derived depolymerases have been used to treat bacterial infections in animals and humans, as in the case of the “San Diego patient” treated with a phage cocktail. Here, we showed that phage PHB19 and its O91-specific polysaccharide depolymerase Dep6 degraded STEC biofilms and stripped the lipopolysaccharide (LPS) from STEC strain HB10, which was subsequently killed by serum complement in vitro. In a mouse model, PHB19 and Dep6 protected against STEC infection and caused a significant reduction in the levels of proinflammatory cytokines. This study reports the use of an O91-specific polysaccharide depolymerase for the treatment of STEC infection in mice.


Bacteriology ◽  
2020 ◽  
Vol 5 (2) ◽  
pp. 56-70
Author(s):  
E.A. Svetoch ◽  
◽  
I.A. Dyatlov ◽  
N.N. Kartsev ◽  
B.V. Eruslanov ◽  
...  

Shiga-toxin producing Escherichia coli (STEC) strains cause serious and life-threatening diseases, hemorrhagic colitis (HC) and associated hemolytic uremic syndrome (HUS). Antibacterial etiotropic therapy against these diseases are not recommended. There are no vaccines against human HA and HUS. The review provides materials on the design of various types of candidate vaccines against STEC strains and assessment of their immunogenic and protective properties in experiments on laboratory and farm animals. The prospects for the use of inactivated corpuscular and live (vector) vaccines, lipopolysaccharide vaccines, DNA vaccines and nanovaccines, vaccines based on bacterial cell membranes (ghost), as well as vaccines created by reverse vaccinology methods in practice are considered. Key words: STEC, hemorrhagic colitis, immunodominant antigens, shiga toxins, EspA, EspB, Tir, intimine, IgG, sIgA


2019 ◽  
Vol 7 (9) ◽  
pp. 276 ◽  
Author(s):  
Miriam Silva ◽  
Anna Santos ◽  
Leticia Rocha ◽  
Bruna Caetano ◽  
Thais Mitsunari ◽  
...  

Shiga toxin (Stx)–producing Escherichia coli (STEC) and its subgroup enterohemorrhagic E. coli are important pathogens involved in diarrhea, which may be complicated by hemorrhagic colitis and hemolytic uremic syndrome, the leading cause of acute renal failure in children. Early diagnosis is essential for clinical management, as an antibiotic treatment in STEC infections is not recommended. Previously obtained antibodies against Stx1 and Stx2 toxins were employed to evaluate the sensitivity and specificity of the latex Agglutination test (LAT), lateral flow assay (LFA), and capture ELISA (cEIA) for STEC detection. The LAT (mAb Stx1 plus mAb stx2) showed 99% sensitivity and 97% specificity. Individually, Stx1 antibodies showed 95.5% and 94% sensitivity and a specificity of 97% and 99% in the cEIA and LFA assay, respectively. Stx2 antibodies showed a sensitivity of 92% in both assays and a specificity of 100% and 98% in the cEIA and LFA assay, respectively. These results allow us to conclude that we have robust tools for the diagnosis of STEC infections.


2016 ◽  
Vol 14 (1) ◽  
pp. 63-68 ◽  
Author(s):  
MM Akter ◽  
S Majumder ◽  
KH MNH Nazir ◽  
M Rahman

Shiga toxin-producing Escherichia coli (STEC) are zoonotically important pathogen which causes hemorrhagic colitis, diarrhea, and hemolytic uremic syndrome in animals and humans. The present study was designed to isolate and identify the STEC from fecal samples of diarrheic cattle. A total of 35 diarrheic fecal samples were collected from Bangladesh Agricultural University (BAU) Veterinary Teaching Hospital. The samples were primarily examined for the detection of E. coli by cultural, morphological and biochemical characteristics, followed by confirmation of the isolates by Polymerase Chain Reaction (PCR) using gene specific primers. Later, the STEC were identified among the isolated E. coli through detection of Stx-1 and Stx-2 genes using duplex PCR. Out of 35 samples, 25 (71.43%) isolates were confirmed to be associated with E. coli, of which only 7 (28%) isolates were shiga toxin producers, and all of them were positive for Stx-1. However, no Stx-2 positive isolate could be detected. From this study, it may be concluded that cattle can act as a reservoir of STEC which may transmit to human or other animals.J. Bangladesh Agril. Univ. 14(1): 63-68, June 2016


2012 ◽  
Vol 75 (2) ◽  
pp. 408-418 ◽  
Author(s):  
LOTHAR BEUTIN ◽  
ANNETT MARTIN

An outbreak that comprised 3,842 cases of human infections with enteroaggregative hemorrhagic Escherichia coli (EAHEC) O104:H4 occurred in Germany in May 2011. The high proportion of adults affected in this outbreak and the unusually high number of patients that developed hemolytic uremic syndrome makes this outbreak the most dramatic since enterohemorrhagic E. coli (EHEC) strains were first identified as agents of human disease. The characteristics of the outbreak strain, the way it spread among humans, and the clinical signs resulting from EAHEC infections have changed the way Shiga toxin–producing E. coli strains are regarded as human pathogens in general. EAHEC O104:H4 is an emerging E. coli pathotype that is endemic in Central Africa and has spread to Europe and Asia. EAHEC strains have evolved from enteroaggregative E. coli by uptake of a Shiga toxin 2a (Stx2a)–encoding bacteriophage. Except for Stx2a, no other EHEC-specific virulence markers including the locus of enterocyte effacement are present in EAHEC strains. EAHEC O104:H4 colonizes humans through aggregative adherence fimbrial pili encoded by the enteroaggregative E. coli plasmid. The aggregative adherence fimbrial colonization mechanism substitutes for the locus of enterocyte effacement functions for bacterial adherence and delivery of Stx2a into the human intestine, resulting clinically in hemolytic uremic syndrome. Humans are the only known natural reservoir known for EAHEC. In contrast, Shiga toxin–producing E. coli and EHEC are associated with animals as natural hosts. Contaminated sprouted fenugreek seeds were suspected as the primary vehicle of transmission of the EAHEC O104:H4 outbreak strain in Germany. During the outbreak, secondary transmission (human to human and human to food) was important. Epidemiological investigations revealed fenugreek seeds as the source of entry of EAHEC O104:H4 into the food chain; however, microbiological analysis of seeds for this pathogen produced negative results. The survival of EAHEC in seeds and the frequency of human carriers of EAHEC should be investigated for a better understanding of EAHEC transmission routes.


2017 ◽  
Vol 61 (9) ◽  
Author(s):  
Andreas Bauwens ◽  
Lisa Kunsmann ◽  
Helge Karch ◽  
Alexander Mellmann ◽  
Martina Bielaszewska

ABSTRACT Ciprofloxacin, meropenem, fosfomycin, and polymyxin B strongly increase production of outer membrane vesicles (OMVs) in Escherichia coli O104:H4 and O157:H7. Ciprofloxacin also upregulates OMV-associated Shiga toxin 2a, the major virulence factor of these pathogens, whereas the other antibiotics increase OMV production without the toxin. These two effects might worsen the clinical outcome of infections caused by Shiga toxin-producing E. coli. Our data support the existing recommendations to avoid antibiotics for treatment of these infections.


2006 ◽  
Vol 69 (1) ◽  
pp. 6-11 ◽  
Author(s):  
L. SCOTT ◽  
P. McGEE ◽  
J. J. SHERIDAN ◽  
B. EARLEY ◽  
N. LEONARD

Escherichia coli O157:H7 is an important foodborne pathogen that can cause hemorrhagic colitis and hemolytic uremic syndrome. Cattle feces and fecally contaminated water are important in the transmission of this organism on the farm. In this study, the survival of E. coli O157:H7 in feces and water was compared following passage through the animal digestive tract or preparation in the laboratory. Feces were collected from steers before and after oral inoculation with a marked strain of E. coli O157:H7. Fecal samples collected before cattle inoculation were subsequently inoculated with the marked strain of E. coli O157:H7 prepared in the laboratory. Subsamples were taken from both animal and laboratory-inoculated feces to inoculate 5-liter volumes of water. E. coli O157:H7 in feces survived up to 97 days, and survival was not affected by the method used to prepare the inoculating strain. E. coli O157:H7 survived up to 109 days in water, and the bacteria collected from inoculated cattle were detected up to 10 weeks longer than the laboratory-prepared culture. This study suggests that pathogen survival in low-nutrient conditions may be enhanced by passage through the gastrointestinal tract.


2000 ◽  
Vol 63 (6) ◽  
pp. 819-821 ◽  
Author(s):  
DAVID W. K. ACHESON

Escherichia coli O157:H7 is but one of a group of Shiga toxin-producing E. coli (STEC) that cause both intestinal disease such as bloody and nonbloody diarrhea and serious complications like hemolytic uremic syndrome (HUS). While E. coli O157: H7 is the most renowned STEC, over 200 different types of STEC have been documented in meat and animals, at least 60 of which have been linked with human disease. A number of studies have suggested that non-O157 STEC are associated with clinical disease, and non-O157 STEC are present in the food supply. Non-O157 STEC, such as O111 have caused large outbreaks and HUS in the United States and other countries. The current policy in the United States is to examine ground beef for O157:H7 only, but restricting the focus to O157 will miss other important human STEC pathogens.


2006 ◽  
Vol 74 (8) ◽  
pp. 4685-4693 ◽  
Author(s):  
Haiqing Sheng ◽  
Ji Youn Lim ◽  
Hannah J. Knecht ◽  
Jie Li ◽  
Carolyn J. Hovde

ABSTRACT The human pathogen Escherichia coli O157:H7 causes hemorrhagic colitis and life-threatening sequelae and transiently colonizes healthy cattle at the terminal rectal mucosa. This study analyzed virulence factors important for the clinical manifestations of human E. coli O157:H7 infection for their contribution to the persistence of E. coli in cattle. The colonizing ability of E. coli O157:H7 was compared with those of nonpathogenic E. coli K-12 and isogenic deletion mutants missing Shiga toxin (Stx), the adhesin intimin, its receptor Tir, hemolysin, or the ∼92-kb pO157. Fully ruminant steers received a single rectal application of one E. coli strain so that effects of mucosal attachment and survival at the terminal rectum could be measured without the impact of bacterial passage through the entire gastrointestinal tract. Colonization was monitored by sensitive recto-anal junction mucosal swab culture. Nonpathogenic E. coli K-12 did not colonize as well as E. coli O157:H7 at the bovine terminal rectal mucosa. The E. coli O157:H7 best able to persist had intimin, Tir, and the pO157. Strains missing even one of these factors were recovered in lower numbers and were cleared faster than the wild type. In contrast, E. coli O157:H7 strains that were missing Stx or hemolysin colonized like the wild type. For these three strains, the number of bacteria increased between days 1 and 4 postapplication and then decreased slowly. In contrast, the numbers of noncolonizing strains (K-12, Δtir, and Δeae) decreased from the day of application. These patterns consistently predicted long-term colonization or clearance of the bacteria from the bovine terminal rectal mucosa.


1992 ◽  
Vol 55 (7) ◽  
pp. 555-565 ◽  
Author(s):  
NISHA V. PADHYE ◽  
MICHAEL P. DOYLE

Escherichia coli O157:H7 is now recognized as an important human pathogen. Illnesses caused by E. coli O157:H7 infection can range from self-limited, watery diarrhea to life-threatening manifestations such as hemolytic uremic syndrome or thrombotic thrombocytopenic purpura. The mode of transmission is primarily through food; however, person-to-person transmission also has been identified in some day-care center and nursing home out-breaks. Studies to date indicate that cattle are an important reservoir of the organism. Although adhesion to intestinal epithelial cells and verotoxins are considered important virulence factors in the pathogenesis of the organism, more research is are necessary to determine the exact mechanism of pathogenicity. There is need for a rapid diagnostic test for the detection of E. coli O157:H7 in food and in clinical samples. Several useful research reagents have been developed for detecting E. coli O157:H7; however, they must be applied to a procedure that is specific, sensitive, rapid, easy to use, and commercially available so that microbiological laboratories can readily use them.


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