Enterocolitica Infection Research Articles

Yersinia enterocolitica infection among children aged less than 12 years: a case–control study

A case-control study was conducted to identify risk factors, signs, and symptoms that may be associated with, Yersinia enterocolitica among children aged less than 12 years. From February 2006 to January 2007, stool samples from diarrhea cases with a clinical diagnosis of gastroenteritis and those of matched uninfected and infected controls, were examined for the presence of Y. enterocolitica. Sixteen sporadic cases of Y. enterocolitica were identified. Of these, eight were detected in winter (December through February), while the remaining cases occurred in the spring, summer, and autumn. Of the 16 isolates, 10 belonged to serotype O:3, five belonged to serotype O:9, and one to serotype O:8. Compared to matched uninfected controls, multivariate analysis revealed that malnutrition (adjusted odds ratio (aOR) 6.23; p=0.002) and water supply (aOR 3.05; p=0.049) were independently associated with infection. Compared to infected controls, multivariate analysis showed malnutrition (aOR 3.53; p=0.027) to be an independent risk factor for the acquisition of yersiniosis. The antibiotic susceptibility profile showed that Y. enterocolitica was generally susceptible to meropenem (100%), ceftriaxone (94%), and ciprofloxacin (94%), followed by ceftazidime (88%) and amikacin (81%). Almost all Y. enterocolitica was resistant to ampicillin. This study demonstrated that Y. enterocolitica occurs sporadically in children, with a predominance of serotypes O:3 and O:9. Furthermore malnutrition was identified as the main risk factor for yersiniosis.

Yersinia Enterocolitica Infection Presenting as Left Lower Quadrant Pain

Yersinia Enterocolitica Infection Presenting as Left Lower Quadrant Pain

Prevalence of pathogenic Yersinia enterocolitica strains on liver surfaces of pigs and their antimicrobial susceptibility.

A study to determine the occurrence of pathogenic Yersinia enterocolitica on surfaces of slaughtered pig livers and the antimicrobial resistant pattern of the isolates was carried out in a slaughterhouse in Lower Saxony, Germany. During the slaughtering process, 1,500 surfaces of pig livers from 50 fattening herds were swabbed in order to isolate and characterize Y. enterocolitica isolates by serotyping, detecting the virulence plasmid coding the yopT gene, and resistance testing. Of the livers tested, 4.7% were positive for Y. enterocolitica O:3, which was the only identified serotype. The virulence gene yopT was found in 90.0% of these isolates. Antimicrobial susceptibility was tested by the broth dilution method, and the MICs were determined for 13 antimicrobials. All isolates were resistant to ampicillin and sulfamethoxazole but were susceptible to ciprofloxacin, nalidixic acid, gentamicin, ceftiofur, tetracycline, kanamycin, cefotaxime, and chlorphenicol. Up to now, resistance to florfenicol has always been described in combination with resistance to chloramphenicol. In the present study, 15.3% of the isolates were resistant to florfenicol, while no chloramphenicol-resistant strains could be identified. Multiresistance to three or more antimicrobials was detected in 22 strains (27.3%). Nevertheless, third-generation cephalosporines or fluoroquinolones, which were recommended for extraintestinal Y. enterocolitica infection in humans, were not affected.

Epidemiology of reported Yersinia enterocolitica infections in Germany, 2001-2008

BackgroundYersiniosis is the third most common zoonotic bacterial disease in Germany and the European Union. Sequelae of Yersinia enterocolitica infections, such as reactive arthritis, have been reported. Consumption of pork and its products, especially eaten raw or undercooked, is an important risk factor of yersiniosis. Infection with Y. enterocolitica is notifiable through the national surveillance system for infectious diseases in Germany and several thousands of cases are being reported each year. We present recent data on the epidemiology of reported yersiniosis in Germany.MethodsSurveillance data on yersiniosis, accessed through the national level database (SurvNet), were analyzed with regard to time trends, demographical and geographical distribution, serotypes, and hospitalization, for the time period 2001-2008.ResultsA total of 47,627 cases of yersiniosis were reported. The mean annual incidence of yersiniosis was 7.2/100,000 population. A downward trend in the number of reportable cases has occurred since 2002. Almost all Y. enterocolitica infections were reported as single cases, i.e., with no apparent links to other cases. The number of reported infections showed substantially less seasonal variation than in other zoonotic enteric diseases. The incidence was highest in children under five years (58/100,000 population), in particular in one-year-old children (108/100,000 population). Almost 97% of infections were acquired domestically. High incidences occurred in the eastern German federal states Thuringia, Saxony, and Saxony-Anhalt. Differences in incidences across federal states were driven primarily by incidence differences in children under five years. Hospitalization was reported for 17% of cases, the proportion being highest among teenagers. Almost 90% of Y. enterocolitica strains were diagnosed as serotype O:3, which is the serotype most frequently isolated from pigs.ConclusionsYersiniosis is a zoonotic foodborne disease of relevance to public health in Germany because of its high incidence and risk for sequelae. The incidence of reported yersiniosis in Germany varies markedly from state to state, mainly due to incidence difference among young children. More research efforts should be directed towards the elucidation of risk factors of yersiniosis in this age group.

Yersinia enterocoliticaPromotes Robust Mucosal Inflammatory T-Cell Immunity in Murine Neonates

Mucosal immunity to gastrointestinal pathogens in early life has been studied only slightly. Recently, we developed an infection model in murine neonates using the gastroenteric pathogen Yersinia enterocolitica. Here, we report that oral infection of neonatal mice with low doses of virulent Y. enterocolitica leads to vigorous intestinal and systemic adaptive immunity. Y. enterocolitica infection promoted the development of anti-LcrV memory serum IgG1 and IgG2a responses of comparable affinity and magnitude to adult responses. Strikingly, neonatal mesenteric lymph node CD4(+) T cells produced Yersinia-specific gamma interferon (IFN-gamma) and interleukin-17A (IL-17A), exceeding adult levels. The robust T- and B-cell responses elicited in neonates exposed to Y. enterocolitica were associated with long-term protection against mucosal challenge with this pathogen. Using genetically deficient mice, we found that IFN-gamma and CD4(+) cells, but not B cells, are critical for protection of neonates during primary Y. enterocolitica infection. In contrast, adults infected with low bacterial doses did not require either cell population for protection. CD4-deficient neonatal mice adoptively transferred with CD4(+) cells from wild-type, IFN-gamma-deficient, or IL-17AF-deficient mice were equally protected from infection. These data demonstrate that inflammatory CD4(+) T cells are required for protection of neonatal mice and that this protection may not require CD4-derived IFN-gamma, IL-17A, or IL-17F. Overall, these studies support the idea that Y. enterocolitica promotes the development of highly inflammatory mucosal responses in neonates and that intestinal T-cell function may be a key immune component in protection from gastrointestinal pathogens in early life.

Identification of Outer Membrane Porin F Protein ofYersinia enterocoliticaRecognized by Antithyrotopin Receptor Antibodies in Graves’ Disease and Determination of Its Epitope Using Mass Spectrometry and Bioinformatics Tools

In addition to genetic susceptibility, Yersinia enterocolitica (YE) infection played an important causative role in the pathogenesis of Graves' disease (GD) through molecular mimicry. However, the specific YE proteins and epitopes recognized by anti-TSH receptor (TSHR) autoantibodies (TRAb) have not been fully clarified, resulting in conflicting results from clinical research. Our aim was to explore the roles of YE in the pathogenesis of GD and identify the YE proteins and epitopes that are similar to the TSHR and are recognized by TRAb. Assays of YE antibodies, TRAb, thyroglobulin antibodies, and thyroid microsomal antibodies as well as cross-absorption and two-way immunodiffusion were performed in patients with GD. Using mass spectrometry and the bioinformatics tools of protein structure modeling and epitope prediction, we identified the YE protein and its epitope, which was recognized by TRAb and was similar to TSHR. Our study demonstrated for the first time that the YE protein outer membrane porin F protein (ompF) shared cross-immunogenicity with a leucine-rich domain of TSHR. The epitope recognized by antihuman TSHR antibody is located within the ompF region of amino acids 190-197, and the polyantibody against ompF protein showed TSAb activity. Our results suggest that YE ompF is involved in the production of TRAb and the pathogenesis of GD through molecular mimicry. These findings are potentially important for understanding the role molecular mimicry plays in the disturbance of immune tolerance and the induction of autoimmunity to the TSHR.

Yersinia pseudotuberculosisandY. enterocoliticaInfections, FoodNet, 1996–2007

<i>Yersinia pseudotuberculosis</i>and<i>Y. enterocolitica</i>Infections, FoodNet, 1996–2007

Intussusception Caused by Yersinia enterocolitica Enterocolitis in a Patient with Sickle Cell Anemia

Yersinia enterocolitica intussusception is rarely encountered in patients without an underlying susceptibility and is most frequently reported in iron-overloaded patients. This is thought to be related to the unusual use of iron by this microorganism. We present a case of a 5-year old child with intussusception of the terminal ileum caused by Y. enterocolitica whose past medical history was significant for sickle cell disease. This type of presentation is extremely rare. His monthly blood transfusions may have put him at risk for Y. enterocolitica enterocolitis. The pathogenesis of this disease relates to the role of iron as an essential growth factor for Y. enterocolitica, and this patient's transfusions left him in an iron overloaded state despite treatment with Deferoxamine. Our patient's unusual presentation of intusssuception was secondary to the mass effect caused by lymphoid hyperplasia, specifically hypertrophied Peyer's patches in the ileum caused by the Y. enterocolitica infection. We believe that our case demonstrates that Y. enterocolitica should be considered a possible pathogen in patients with sickle cell disease, especially if symptoms occur shortly after blood transfusion.

Evaluation of ELISA in the diagnosis of Yersinia enterocolitica diarrhoea in children.

In a series of acute gastroenteritis in children, including 2 bacteriologically confirmed cases of Yersinia enterocolitica infection, paired sera from 286 patients were studied for the presence of Y. enterocolitica 0:3 and 0:9 antibodies, using an enzyme-linked immunosorbent assay (ELISA). In the 2 cases with positive stool culture of Y. enterocolitica 0:3 significant rise was seen in each IgM, IgG and IgA class Y. enterocolitica 0:3 antibodies. There were 6 further cases with elevated anti-Yersinia IgM: these possibly false-positive reactions were distinguished from the confirmed cases of Y. enterocolitica infection by the absence of IgG and IgA antibodies.

Is the Yersinia enterocolitica Possible Infectious Agent in Acute Appendicitis?

Purpose: With increasing frequency, Yersinia enterocolitica is being recognized as an important bacterial cause of acute gastrointestinal infection with abdominal pain. In addition, the association of Y. enterocolitica infections with acute appendicitis has been suggested. This study was undertaken to ascertain whether Y. enterocolitica is a possible infectious agent in acute appendicitis. Methods: Between December 2007 and April 2008, 162 patients who underwent appendectomy for presumed appendicitis, enrolled in this prospective study. After surgical excision of appendix, a portion of each specimen was cultured for Y. enterocolitica with highly selective media (Cefsulodin-Irgasan-Novobiocin agar). Results: Pathologically, 150 of the patients had appendicitis and 12 patients had normal appendices. Only one of the 150 patients (0.7%) with appendicitis was found to be culture positive for Y. enterocolitica, while it was not detected from normal appendices. Conclusion: The authors were unable to implicate Y. enterocolitica as a major pathogen in acute appendicitis within the Seoul area. However, we thought there to be more need for investigation for association of Y. enterocolitica with acute appendicitis over a broader area and season.

Yersinia enterocolitica infection of murine neonates: A model of pediatric inflammatory bowel disease

Yersinia enterocolitica infection of murine neonates: A model of pediatric inflammatory bowel disease

Interleukin-12p40 contributes to protection against lung injury after oral Yersinia enterocolitica infection

The impact of Yersinia enterocolitica on lung is incompletely understood, so we studied the inflammatory effects of Yersinia oral infection and the influence of IL-12p40 deficiency. Wild-type (WT) and IL-12p40-/- (KO) mice were orally infected with Y. enterocolitica 0:3. After 3 and 21 days, cell viability in bronchoalveolar lavage (BAL) fluid, inflammatory reactions, lipid hydroperoxides, antioxidant enzyme expression and histological changes were studied. An effect on the lung was demonstrated by changes in lactate dehydrogenase, total protein (p <0.001), nitrosative stress and increase numbers of lymphocyte in the BAL fluid. All of these appeared to be IL-12 - independent since statistically significant changes in response to infection (at 21 days) did not differ between WT and KO groups. However, a protective role of IL-12 after infection was suggested by a decrease in cell viability, histopathological changes, different cell populations, higher lipid peroxidation and a decrease in antioxidant enzymes - glutathione peroxidase, superoxide dismutase-2 (p <0.05). The main changes were detected at day 21 suggesting a chronic effect of Yersinia infection and that IL-12 could play a role in the protection against chronic sequelae in the lung. These results demonstrate that Y. enterocolitica infection may induce inflammatory response in lung and that IL-12p40 could contribute to protection against lung injury.

Role of connexin-43 hemichannels in the pathogenesis of Yersinia enterocolitica

Connexin (Cx) channels are sites of cytoplasmic communication between contacting cells. Evidence indicates that the opening of hemichannels occurs under both physiological and pathological conditions. In this paper, the involvement of Cx-43 hemichannels is demonstrated in the pathogenesis of Yersinia. Parental HeLa cells and transfected HeLa cells stably expressing Cx-43 (HCx43) were infected with Yersiniaenterocolitica, and bacterial uptake was measured by the colony-forming unit method. Bacterial uptake was higher in HCx43 cells than in parental cells and was inhibited by the Cx channel blocker, 18-alpha-glycyrrhetinic acid (AGA). The inhibitory effect of AGA was more pronounced on the Y. enterocolitica uptake by HCx43 cells than by parental cells. The ability of HCx43 cells to incorporate the permeable fluorescent tracer Lucifer Yellow (LY) was assessed. Dye incorporation was inhibited by AGA, whereas Y. enterocolitica infection of HCx43 cells increased LY incorporation. Western blotting analysis demonstrated that Y. enterocolitica infection of HCx43 cells induced tyrosine phosphorylation of Cx-43, thus supporting a critical role for Cx-43 in the strategies exploited by bacterial pathogens to invade non-phagocytic cells.

Sources of sporadic Yersinia enterocolitica infection in children in Sweden, 2004: a case-control study

Young children account for a large proportion of reported Yersinia enterocolitica infections in Sweden with a high incidence compared with other gastrointestinal infections, such as salmonellosis and campylobacteriosis. A case-control study was conducted to investigate selected risk factors for domestic sporadic yersiniosis in children aged 0-6 years in Sweden. In total, 117 cases and 339 controls were included in the study. To minimize exclusion of observations due to missing data a multiple non-parametric imputation technique was used. The following risk factors were identified in the multivariate analysis: eating food prepared from raw pork products (OR 3.0, 95% CI 1.8-5.1) or treated sausage (OR 1.9, 95% CI 1.1-3.3), use of a baby's dummy (OR 1.9, 95% CI 1.1-3.2) and contact with domestic animals (OR 2.0, 95% CI 1.2-3.4). We believe that the importance of Y. enterocolitica infection in children has been neglected and that results from this study can be used to develop preventive recommendations.

Too early to dismiss Yersinia enterocolitica infection in the aetiology of Graves’ disease: evidence from a twin case–control study

Yersinia enterocolitica (YE) infection has long been implicated in the pathogenesis of Graves' disease (GD). The association between YE and GD could, however, also be due to common genetic or environmental factors affecting the development of both YE infection and GD. This potential confounding can be minimized by investigation of twin pairs discordant for GD. To examine whether YE infection is associated with GD. We first conducted a classical case-control study of individuals with (61) and without (122) GD, and then a case-control study of twin pairs (36) discordant for GD. Immunoglobulin (Ig)A and IgG antibodies to virulence-associated Yersinia outer membrane proteins (YOPs) were measured. The prevalence of YOP IgA and IgG antibodies. Subjects with GD had a higher prevalence of YOP IgA (49%vs. 34%, P = 0.054) and YPO IgG (51%vs. 35%, P = 0.043) than the external controls. The frequency of chronic YE infection, reflected by the presence of both IgA and IgG YOP antibodies, was also higher among cases than controls (49%vs. 33%, P = 0.042). Similar results were found in twin pairs discordant for GD. In the case-control analysis, individuals with GD had an increased odds ratio (OR) of YE infection: IgA 1.84 (95% CI 0.99-3.45) and IgG 1.90 (95% CI 1.02-3.55). In the co-twin analysis, the twin with GD also had an increased OR of YE infection: IgA 5.5 (95% CI 1.21-24.81) and IgG 5.0 (95% CI 1.10-22.81). The finding of an association between GD and YE in the case-control study and within twin pairs discordant for GD supports the notion that YE infection plays an aetiological role in the occurrence of GD, or vice versa. Future studies should examine the temporal relationship of this association in more depth.

Yersinia enterocolitica infection in diarrheal patients

In this study, we hoped to provide valuable clinical information on yersiniosis for clinicians. Two thousand six hundred stool samples were collected from in- and outpatients with diarrhea, which were tested with both culture method and real-time polymerase chain reaction (RT-PCR). In total, 188 positive samples were detected by RT-PCR (178) and culture method (160), while the incidence was about 7.23%. The detection rate of RT-PCR was significantly higher than culture method and a higher incidence in autumn-winter was also noticeably identified than in spring-summer. Infection sources mostly focused on unboiled foods (101) and pets (45), while clinical manifestation mainly presented as gastroenteritis (156), pseudoappendicitis (32), and extraintestinal complications (46). The morbidity of extraintestinal complications in adults was significantly higher than in children and it was the same for high-risk patients between adults over the age of 60 years (4.7%) and children under the age of 3 years (1.4%), whereas the constituent ratio of children versus adults with yersiniosis in different systems was not significant. Of 160 isolates tested for antimicrobial susceptibility, the majority were susceptible to third-generation cephalosporins, aminoglycosides, fluoroquinolones, and trimethoprim-sulfamethoxazole, whereas only a small portion was susceptible to the first-generation cephalosporins and penicillins. During autumn-winter months, clinicians should pay more attention to clinical manifestation, early diagnosis, and treatment with susceptible antibiotics of yersiniosis and its complications, targeting high-risk patients.

Reduced Secretion of YopJ by Yersinia Limits In Vivo Cell Death but Enhances Bacterial Virulence

Numerous microbial pathogens modulate or interfere with cell death pathways in cultured cells. However, the precise role of host cell death during in vivo infection remains poorly understood. Macrophages infected by pathogenic species of Yersinia typically undergo an apoptotic cell death. This is due to the activity of a Type III secreted effector protein, designated YopJ in Y. pseudotuberculosis and Y. pestis, and YopP in the closely related Y. enterocolitica. It has recently been reported that Y. enterocolitica YopP shows intrinsically greater capacity for being secreted than Y. pestis YopJ, and that this correlates with enhanced cytotoxicity observed for high virulence serotypes of Y. enterocolitica. The enzymatic activity and secretory capacity of YopP from different Y. enterocolitica serotypes have been shown to be variable. However, the underlying basis for differential secretion of YopJ/YopP, and whether reduced secretion of YopJ by Y. pestis plays a role in pathogenesis during in vivo infection, is not currently known. It has also been reported that similar to macrophages, Y. enterocolitica infection of dendritic cells leads to YopP-dependent cell death. We demonstrate here that in contrast to Y. enterocolitica, Y. pseudotuberculosis infection of bone marrow–derived dendritic cells does not lead to increased cell death. However, death of Y. pseudotuberculosis–infected dendritic cells is enhanced by ectopic expression of YopP in place of YopJ. We further show that polymorphisms at the N-terminus of the YopP/YopJ proteins are responsible for their differential secretion, translocation, and consequent cytotoxicity. Mutation of two amino acids in YopJ markedly enhanced both translocation and cytotoxicity. Surprisingly, expression of YopP or a hypersecreted mutant of YopJ in Y. pseudotuberculosis resulted in its attenuation in oral mouse infection. Complete absence of YopJ also resulted in attenuation of virulence, in accordance with previous observations. These findings suggest that control of cytotoxicity is an important virulence property for Y. pseudotuberculosis, and that intermediate levels of YopJ-mediated cytotoxicity are necessary for maximal systemic virulence of this bacterial pathogen.

Resistance of Chemokine Receptor 6-Deficient Mice to Yersinia Enterocolitica Infection : Evidence of Defective M-Cell Formation in Vivo

M cells, specialized cells within Peyer's patches (PPs), are reduced in number in chemokine receptor 6 (CCR6)-deficient mice. The pathogenic microorganism Yersinia enterocolitica exploits M cells for the purpose of mucosal tissue invasion exclusively through PPs. The aim of this study was to evaluate the course of yersiniosis in CCR6-deficient mice and to investigate whether these mice might be used as an in vivo model to determine M-cell function. After oral challenge with Y. enterocolitica, control mice suffered from lethal septic infection whereas CCR6-deficient mice showed very limited symptoms of infection. Immunohistochemical analysis demonstrated PP invasion by Y. enterocolitica in control mice whereas no bacteria could be found in CCR6-deficient mice. In addition, a significant induction of proinflammatory cytokines could be found in control mice whereas proinflammatory cytokine levels in CCR6-deficient mice remained unchanged. In contrast, intraperitoneal infection resulted in severe systemic yersiniosis in both mouse groups. Abrogated oral Y. enterocolitica infection in CCR6-deficient mice demonstrates the importance of CCR6 expression in the physiological and pathological immune responses generated within PPs by influencing M-cell differentiation, underscoring the important role of M cells in the process of microbial uptake. CCR6-deficient mice may therefore represent a suitable model for the study of M-cell function in vivo.

Hypoxia-Independent Activation of HIF-1 by Enterobacteriaceae and Their Siderophores

Hypoxia inducible factor-1 (HIF-1) is the key transcriptional regulator during adaptation to hypoxia. Recent studies provide evidence for HIF-1 activation during bacterial infections. However, molecular details of how bacteria activate HIF-1 remain unclear. Here, we pursued the role of bacterial siderophores in HIF-1 activation during infection with Enterobacteriaceae. In vivo, HIF-1 activation and HIF-1-dependent gene induction in Peyer's patches were analyzed after orogastric infection with Yersinia enterocolitica. The course of an orogastric Y enterocolitica infection was determined using mice with a deletion of HIF-1alpha in the intestine. In vitro, the mechanism of HIF-1 activation was analyzed in infections with Y enterocolitica, Salmonella enterica subsp enterica, and Enterobacter aerogenes. Infection of mice with Y enterocolitica led to functional activation of HIF-1 in Peyer's patches. Because mice with deletion of HIF-1alpha in the intestinal epithelium showed a significantly higher susceptibility to orogastric Y enterocolitica infections, bacterial HIF-1 activation appears to represent a host defense mechanism. Additional studies with Y enterocolitica, S enterica subsp enterica, or E aerogenes, and, moreover, application of their siderophores (yersiniabactin, salmochelin, aerobactin) caused a robust, dose-dependent HIF-1 response in human epithelia and endothelia, independent of cellular hypoxia. HIF-1 activation occurs most likely because of inhibition of prolylhydroxylase activity and is abolished upon infection with siderophore uptake deficient bacteria. Taken together, this study reveals what we believe to be a previously unrecognized role of bacterial siderophores for hypoxia-independent activation of HIF-1 during infection with human pathogenic bacteria.

Yersinia enterocolitica-associated generalized microinfarctions of bone and spleen in a child

We report a case of unusual extraintestinal yersiniosis in a 16-year-old girl with generalized microinfarctions of the bone and spleen. For the past 2 years she had been repeatedly admitted to our hospital with reactive arthritis, erythema nodosum and iridocyclitis of unknown aetiology. Ultrasound showed multiple round hypoechoic lesions in the spleen that were shown to have low T2 signal on MRI. MRI also showed disseminated nodular lesions of the skeleton that were low T1 and high T2 signal and demonstrated inhomogeneous contrast enhancement. The patient is currently in good health on low-dose nonsteroidal immunosuppressive therapy. This is a unique case of microinfarctions of the skeleton and spleen caused by a severe postinfectious autoimmune reaction following extraintestinal Yersinia enterocolitica infection.