Dopamine receptor D2 confers colonization resistance via microbial metabolites.

The gut microbiome has major roles in modulating host physiology. One such function is colonization resistance, or the ability of the microbial collective to protect the host against enteric pathogens1-3, including enterohaemorrhagic Escherichia coli (EHEC) serotype O157:H7, an attaching and effacing (AE) food-borne pathogen that causes severe gastroenteritis, enterocolitis, bloody diarrhea and acute renal failure4,5 (haemolytic uremic syndrome). Although gut microorganisms can provide colonization resistance by outcompeting some pathogens or modulating host defence provided by the gut barrier and intestinal immune cells6,7, this phenomenon remains poorly understood. Here, we show that activation of the neurotransmitter receptor dopamine receptor D2 (DRD2) in the intestinal epithelium by gut microbial metabolites produced upon dietary supplementation with the essential amino acid L-tryptophan protects the host against Citrobacter rodentium, a mouse AE pathogen that is widely used as a model for EHEC infection8,9. We further find that DRD2 activation by these tryptophan-derived metabolites decreases expression of a host actin regulatory protein involved in C. rodentium and EHEC attachment to the gut epithelium via formation of actin pedestals. Our results reveal a noncanonical colonization resistance pathway against AE pathogens that features an unconventional role for DRD2 outside the nervous system in controlling actin cytoskeletal organization in the gut epithelium. Our findings may inspire prophylactic and therapeutic approaches targeting DRD2 with dietary or pharmacological interventions to improve gut health and treat gastrointestinal infections, which afflict millions globally.

The yad and yeh fimbrial loci influence gene expression and virulence in enterohemorrhagic Escherichia coli O157:H7.

Fimbriae are essential virulence factors for many bacterial pathogens. Fimbriae are extracellular structures that attach bacteria to surfaces. Thus, fimbriae mediate a critical step required for any pathogen to establish infection by anchoring a bacterium to host tissue. The human pathogen enterohemorrhagic Escherichia coli (EHEC) O157:H7encodes 16 fimbriae that may be important for EHEC to initiate infection and allow for productive expression of virulence traits important in later stages of infection, including a type III secretion system (T3SS) and Shiga toxin; however, the roles of most EHEC fimbriae are largely uncharacterized. Here, we provide evidence that two EHEC fimbriae, Yad and Yeh, modulate expression of diverse genes including genes encoding T3SS and Shiga toxin and that these fimbriae are required for robust colonization of the gastrointestinal tract. These findings reveal a significant and previously unappreciated role for fimbriae in bacterial pathogenesis as important determinants of virulence gene expression.IMPORTANCEFimbriae are extracellular proteinaceous structures whose defining role is to anchor bacteria to surfaces. This is a fundamental step for bacterial pathogens to establish infection in a host. Here, we show that the contributions of fimbriae to pathogenesis are more complex. Specifically, we demonstrate that fimbriae influence expression of virulence traits essential for disease progression in the intestinal pathogen enterohemorrhagic Escherichia coli. Gram-positive and Gram-negative bacteria express multiple fimbriae; therefore, these findings may have broad implications for understanding how pathogens use fimbriae, beyond adhesion, to initiate infection and coordinate gene expression, which ultimately results in disease.

Occurrence, molecular characterization, and antimicrobial susceptibility of sorbitol non-fermenting Escherichia coli in lake water, fish and humans in central Oromia, Ethiopia.

Contaminated lake water and fish can be sources of bacterial pathogens of public health concern, including pathogenic E. coli. Within Ethiopia, specifically, Central Oromia, raw fish consumption is a common practice. Although there are few reports on occurrence of E. coli O157 in fish destined for human consumption and children under five years, information on the transmission pathways of E. coli O157 and other sorbitol non-fermenting (SN-F) E. coli from water-to-fish-to-human, and their virulence factors and antimicrobial resistant determinants along the fish supply chain is lacking. The study aimed to investigate the occurrence, molecular characteristics, and antimicrobial susceptibility of E. coli O157 and other SN-F E. coli strains in fish, lake water and humans in central Oromia, Ethiopia. A total of 750 samples (450 fish samples, 150 water samples, 150 human stool samples) were collected from five lakes and three health facilities. The samples were processed following the standard protocol recommended by European Food Safety Authority and Kirby-Bauer disc diffusion method for detection of the bacteria, and antimicrobial susceptibility tests, respectively. Molecular characterization of presumptive isolates was performed using Whole-Genome Sequencing (WGS) for serotyping, determination of virulence factors, antimicrobial resistance traits, and genetic linkage of the isolates. Overall, 3.9% (29/750) of the samples had SN-F E. coli; of which 6.7% (n = 10), 1.8% (n = 8) and 7.3% (n = 11) were retrieved from water, fish, and diarrheic human patients, respectively. The WGS confirmed that all the isolates were SN-F non-O157: H7 E. coli strains. We reported two new E. coli strains with unknown O-antigen from fish and human samples. All the strains have multiple virulence factors and one or more genes encoding for them. Genetic relatedness was observed among strains from the same sources (water, fish, and humans). Most isolates were resistant to ampicillin (100%), tetracycline (100%), cefotaxime (100%), ceftazidime (100%), meropenem (100%), nalidixic acid (93.1%) and sulfamethoxazole/trimethoprim (79.3%). Majority of the strains were resistant to chloramphenicol (58.6%) and ciprofloxacin (48.3%), while small fraction showed resistance to azithromycin (3.45%). Isolates had an overall MDR profile of 87.5%. Majority, (62.1%; n = 18) of the strains had acquired MDR traits. Genes encoding for mutational resistance and Extended-spectrum beta-lactamases (ESBL) were also detected. In conclusion, our study revealed the occurrence of virulent and MDR SN-F E. coli strains in water, fish, and humans. Although no genetic relatedness was observed among strains from various sources, the genomic clustering among strains from the same sources strongly suggests the potential risk of transmission along the supply chain at the human-fish-environment interface if strict hygienic fish production is not in place. Further robust genetic study of the new strains with unknown O-antigens, and the epidemiology of SN-F E. coli is required to elucidate the molecular profile and public health implications of the pathogens.

Sorologia e suscetibilidade antimicrobiana em isolados de Escherichia coli de pesque-pagues / Serology and patterns of antimicrobial susceptibility in Escherichia coli isolates from pay-to-fish ponds

Pesquisou-se a ocorrência de Escherichia coli (EPEC, EIEC, O157) em água e peixe (pele, trato digestivo e músculo) de pesque-pagues da microbacia do Córrego Rico, Jaboticabal (SP). Foram isoladas 115 cepas de E. coli, entre as quais 49 (43%) foram sorogrupadas como EPEC. Os sorogrupos mais frequentes foram O125, O126 e O158. Dentre as amostras testadas, 60 (52%) apresentaram resistência simultânea a dois antimicrobianos. A análise de correspondência foi realizada com o intuito de verificar as possíveis correspondências envolvendo o local de isolamento, sorogrupos e multirresistência e, com isso, pôde-se observar que o músculo apresentou menor correspondência com os demais fatores analisados. Porém, o isolamento de sorogrupos EPEC neste estudo representa risco à saúde dos consumidores.(AU)

The occurrence of Escherichia coli (EPEC, EIEC and O157) in water and fish (skin, gut and muscle) in pay-to-fish ponds of the micro bay of Córrego Rico, in Jaboticabal (SP), was assessed. One hundred and fifteen strains of E. coli were isolated, and 49 (43%) were serogrouped as EPEC. The most common serogroups were O125, O126 and O158. Among the tested samples, 60 (52%) showed simultaneous resistance to two antimicrobials. A correspondence analysis was performed to assess possible correlations involving the site of isolation, serogroups and multi-resistance. The results of this analysis showed that the muscle was less correlated with the the other factors. However, the isolation of EPEC serogroups in this study demonstrates a risk to public health.(AU)

Escherichia coli O157:H7: local epidemiology and disease spectrum in Brazil

Escherichia coli O157: H7 is one of the most important foodborne pathogens nowadays, since it has been responsible for severe outbreaks worldwide. Event hough this food pathogen has been isolated in many countries, Brazilian foods were considered E. coli O157:H7-free until recently. However, the presence of E. coli O157:H7 has been reported in diverse foods produced in Brazil and an increasing number of isolation from cattle feces has been observed, demonstrating that this pathogen is present in different parts of Brazil, and severe foodborne outbreaks mayoccur in the near future if adequate control measures are not implemented

Influence of raw meat natural background flora on growth of Escherichia coli 0157: H7 in ground beef

Escherichia coli 0157 : H7 foodborne pathogen of increasing importance. It has been involved in several threatening outbreaks, most of them associated with meat products. In this study, the influence of some bacteria from the natural background flora of raw meat over E.coli 0157 : H7 in ground beef stored under refrigeration and at room temperature was evaluated. Different levels of E.coli 0157 : H7 (10 1 - 10 2, 10 3 - 10 4, and 10 6 - 10 7 CFU/g), inoculated in ground beef samples, were challenged with strains of non-pathogenic E.coli, Psudomonas putida or Leuconostoc sp. Growth of the pathogen was monitored using standard cultural methods and an Elisa-type rapid method. Non-pathogenic E.coli, Pseudomonas putida and Leuconostoc sp. did not affect growth of E.coli 0157 : H7 in ground beef, both under refrigeration and at room temperature. Based on these findings, the low occurrence of E.coli 0157 : H7 in raw meat may not be attributed to antagonistic effects of bacteria from the natural background flora.

Colitis hemorrágica por escherichia coli enterohemorrágica O157 H:7: comentario en relación a dos casos clínicos / Haemorrhagic colitis caused by escherichia coli H7-O157: a review of 2 clinical cases

Escherichia coli enterohemorrágica O157 H:7 es una infección emergente en nuestro país. Dos casos graves en nuestra unidad permiten actualizar aspectos poco conocidos. A diferencia de países desarrollados (edad media 15 años), en nuestro país afecta a niños pequeños (media 1,5 años) indicando probablemente transmisión doméstica desde el adulto, que no enferma por inmunidad. La colitis puede ser grave y requerir colectomía cuyas indicaciones no son precisas. No está comprobado que los antibióticos aumenten la incidencia de SHU pero se sugiere evitar su uso temprano. No todos los laboratorios clínicos buscan este germen aun cuando la técnica es fácil. El tratamiento debe incluir una observación cuidadosa buscando las complicaciones como síndrome hemolítico urémico y un manejo adecuado de contactos. La prevención se basa en buen lavado de utensilios de cocina en contacto con carne cruda, de las manos antes de tomar o alimentar niños, y la ingestión de carne de vacuno y cerdo bien cocida, en especial si es molida. Proposiciones: el médico debe buscar la etiología, y las autoridades difundir medidas de prevención e instaurar notificación obligatoria

Ocorrência de Escherichia coli O157: H7 em alimentos / Occurrence de Escherichia coli O157: H7 em alimentos

Escherichia coli O157:H7 foi reconhecida como um importante patógeno de origem alimentar no início dos anos 90, quando ocorreram vários surtos, principalmente nos Estados Unidos, envolvendo casos fatais, pelo consumo de produtos cárneos mal cozidos. E. coli O157:H7 provoca doenças graves, incluindo a colite hemorrágica e falhas renais (síndrome urêmica hemolítica). Vários outros, têm sido aplicados à análise rápida em alimentos. Alguns aspectos sobre o organismo, a doença, os alimentos envolvidos säo apresentados e os métodos de detecçäo säo discutidos neste trabalho de revisäo

Impacto del síndrome hemolítico urémico en las distintas áreas de salud de la Región Metropolitana / Impact of the uremic hemolytic syndrome in different health areas of the Región Metropolitana

El síndrome hemolítico urémico (SHU) constituye la causa más frecuente de insuficiencia renal aguda en lactantes y preescolares conocida en el mundo. En Chile, el diagnóstico de SHU ha tenido un aumento significatico en los últimos 10 años. A nivel internacional, el principal agente involucrado en la patogenia del SHU, es la Escherichia coli enterohemorrágica (ECEH, situación que también la hemos comprobado en nuestro país. Para conocer la magnitud del problema, como primer acercamiento, analizamos en el presente trabajo la tasa de incidencia anual de los casos más severos de SHU en la Región Metropolitana (RM), considerando a pacientes residentes en Santiago, que fueron atendidos en diferentes áreas de salud entre el 1 de enero de 1992 y el 31 de diciembre de 1994. En el período de estudio se registraron 61 casos de SHU en niños bajo 5 años de edad en la RM, lo que corresponde a una tasa de incidencia, de 3,26 por 100.000 niños de este grupo etario. El 82 porciente de los casos correspondió a niños entre 4 y 24 meses. Se observaron diferencias en las tasas de incidencia en las distintas áreas de salud, con un rango entre 7,3 y 0,86 por 100.000. En el área de salud Oriente se registró la tasa más elevada de casos de SHU y que fue significativamente mayor (p=<0,01) que en las restantes

Detección de citotoxinas de escherichia coli enterohemorrágica en productos cárnicos chilenos e importados / Detection of shiga-like toxin producing escherichia coli in chilean and imported meat products

Escherichia coli enterohemorrágica (ECEH) está catalogada como un patógeno emergente asociado al consumo de carnes contaminadas. Con el fin de establecer la importancia de los alimentos cárnicos chilenos e importados de venta libre en Santiago de Chile en la transmisión de infecciones por ECEH, se determinó la presencia de citotoxina stx1 y stx2 en dichos alimentos. Se analizaron 213 muestras cárnicas (157 chilenas y 56 importadas) por una prueba de inmunoensayo enzimático Premier, EHEC (Meridian Diagnostics Inc, Cincinnati, U.S.A.). Del total analizado, 9 (4,2 por ciento) muestras que correspondieron a 5 de carne de vacuno chilena, 2 de hamburguesas chilenas y 2 de carne de vacuno paraguaya, presentaron valores positivos a la presencia de citotoxina(s). De acuerdo a estos resultados, es necesario mantener el control microbiológico de ECEH en estos alimentos, con el fin de prevenir la aparición de brotes de intoxicación alimentaria en el país

Microangiopatías trombóticas: SUH/PTT: aspectos fisiopatológicos / Trombotic microangiopathies: SUH/PTT: physiopathological aspects

La causa y mecanismo de la lesión de la célula endotelial (CE) y el mecanismo que provoca la trombosis son los hechos fisiopatológicos más importantes y aún no totalmente conocidos como el Sindrome Urémico Hemolítico/Púrpura Trombocitopénica Trombótica (SUH/PTT). En el SUH asociado a Toxina de Shiga, la lesión de la CE es provocada por la toxina, que penetra a la célula a través de un receptor glicolipídico (Gb3) y altera la síntesis de proteínas celulares a nivel de los ribosomas, provocando la muerte celular por injuria o apoptosis. Existirían mecanismos que amplifican o facilitan la lesión endotelial por la toxina, a través de secreciones de citoquinas inflamatorias, activación de neutrófilos, etc. También se postula que existen factores condicionantes para la aparición de este síndrome, que podrían ser inmunológicos o genéticos. En las otras formas clínicas de SUH/PTT, idiopáticas, secundarias o familiares, tanto esporádicas como recurrentes, el mecanismo de la lesión de la CE no es conocido, pero pueden ser múltiples de acuerdo con cuál sea el cuadro clínico con el que se asocia (idiopático, infecciones, drogas, embarazo, enfermedades autoinmunes, etc.) También podrían existir mecanismos amplificadores de la lesión endotelial (citoquinas) y factores genéticos de predisposición, como el déficit de factor H del complemento en SUH familiar o esporádicos. En cuanto al mecanismo de la trombosis, la lesión o activación de la CE, al disminuir su tromborresistencia y aumentar su capacidad trombogénica, puede inducir la trombosis por múltiples mecanismos (activación de coagulación, activación plaquetaria e hipofibrinolisis). Se enfatizan las alteraciones de su membrana con disminución de los sistemas inhibidores de coagulación, expresión de Factor Tisular, disminución de los sistemas inhibidores de coagulación, expresión de Factor Tisular, disminución del sistema de ectoadepeasa (CD39), la liberación de FvW, etc., como mecanismos trombogénicos relevantes. Las modificaciones del FvW ("multímeros ultragrandes" o "multímeros pequeños") por una alteración en el clivaje de su molécula que genera multímeros con mayor afinidad y actividad agregante plaquetaria, es un mecanismo importante para mantener y aumentar el proceso trombótico, pero no parece ser el único mecanismo trombogénico en esta patología. La descripción reciente de "déficit congénito de la proteasa de FvW" en casos de PTT familiares y de déficit funcional de esta "proteasa"...