RESUMEN
The mechanism whereby Entamoeba histolytica (Eh) binding with macrophages at the intercellular junction triggers aggressive pro-inflammatory responses in disease pathogenesis is not well understood. The host intracellular protein degradation process autophagy and its regulatory proteins are involved in maintenance of cellular homeostasis and excessive inflammatory responses. In this study we unraveled how Eh hijacks the autophagy process in macrophages to dysregulate pro-inflammatory responses. Direct contact of live Eh with macrophages activated caspase-6 that induced rapid proteolytic degradation of the autophagy ATG16L1 protein complex independent of NLRP3 inflammasome and caspase-3/8 activation. Crohn's disease susceptible ATG16L1 T300A variant was highly susceptible to Eh-mediated degradation that augmented pro-inflammatory cytokines in mice. Quantitative proteomics revealed downregulation of autophagy and vesicle-mediated transport and upregulation of cysteine-type endopeptidase pathways in response to Eh. We conclude during Eh-macrophage outside-in signaling, ATG16L1 protein complex plays an overlooked regulatory role in shaping the pro-inflammatory landscape in amebiasis.
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Autofagia , Entamoeba histolytica/fisiología , Entamebiasis/etiología , Entamebiasis/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismo , Transducción de Señal , Animales , Autofagia/inmunología , Biomarcadores , Caspasas/genética , Caspasas/metabolismo , Línea Celular , Biología Computacional , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Entamebiasis/patología , Regulación de la Expresión Génica , Interacciones Huésped-Parásitos/genética , Interacciones Huésped-Parásitos/inmunología , Humanos , Macrófagos/parasitología , Ratones , Proteoma , Proteómica/métodos , Interferencia de ARN , ARN Interferente Pequeño/genéticaAsunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/etiología , Aspergilosis/microbiología , Coccidioidomicosis/microbiología , Entamebiasis/parasitología , Infecciones por VIH/complicaciones , Aspergilosis/etiología , Aspergilosis/patología , Aspergillus/aislamiento & purificación , Coccidioides/aislamiento & purificación , Coccidioidomicosis/etiología , Coccidioidomicosis/patología , Entamoeba histolytica/aislamiento & purificación , Entamebiasis/etiología , Entamebiasis/patología , Resultado Fatal , Humanos , Masculino , Persona de Mediana EdadRESUMEN
These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of intestinal parasites in the pre- and post-transplant period. Intestinal parasites are prevalent in the developing regions of the world. With increasing travel to and from endemic regions, changing immigration patterns, and the expansion of transplant medicine in developing countries, they are increasingly recognized as a source of morbidity and mortality in solid-organ transplant recipients. Parasitic infections may be acquired from the donor allograft, from reactivation, or from de novo acquisition post-transplantation. Gastrointestinal multiplex assays have been developed; some of the panels include testing for Cryptosporidium, Cyclospora, Entamoeba histolytica, and Giardia, and the performance is comparable to conventional methods. A polymerase chain reaction test, not yet widely available, has also been developed to detect Strongyloides in stool samples. New recommendations have been developed to minimize the risk of Strongyloides donor-derived events. Deceased donors with epidemiological risk factors should be screened for Strongyloides and recipients treated if positive as soon as the results are available. New therapeutic agents and studies addressing the optimal treatment regimen for solid-organ transplant recipients are unmet needs.
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Antihelmínticos/uso terapéutico , Selección de Donante/normas , Parasitosis Intestinales/diagnóstico , Parasitosis Intestinales/tratamiento farmacológico , Trasplante de Órganos/efectos adversos , Guías de Práctica Clínica como Asunto/normas , Donantes de Tejidos/provisión & distribución , Animales , Criptosporidiosis/diagnóstico , Criptosporidiosis/tratamiento farmacológico , Criptosporidiosis/etiología , Cryptosporidium/aislamiento & purificación , Cyclospora/aislamiento & purificación , Ciclosporiasis/diagnóstico , Ciclosporiasis/tratamiento farmacológico , Ciclosporiasis/etiología , Equinococosis/diagnóstico , Equinococosis/tratamiento farmacológico , Equinococosis/etiología , Echinococcus/aislamiento & purificación , Entamoeba histolytica/aislamiento & purificación , Entamebiasis/diagnóstico , Entamebiasis/tratamiento farmacológico , Entamebiasis/etiología , Giardia/aislamiento & purificación , Giardiasis/diagnóstico , Giardiasis/tratamiento farmacológico , Giardiasis/etiología , Helmintos/aislamiento & purificación , Humanos , Parasitosis Intestinales/etiología , Microsporidios/aislamiento & purificación , Microsporidiosis/diagnóstico , Microsporidiosis/tratamiento farmacológico , Microsporidiosis/etiología , Schistosoma/aislamiento & purificación , Esquistosomiasis/diagnóstico , Esquistosomiasis/tratamiento farmacológico , Esquistosomiasis/etiología , Sociedades Médicas , Strongyloides/aislamiento & purificación , Estrongiloidiasis/diagnóstico , Estrongiloidiasis/tratamiento farmacológico , Estrongiloidiasis/etiología , Receptores de TrasplantesRESUMEN
OBJECTIVES: To investigate the molecular epidemiology of Entamoeba histolytica, E. dispar and E. moshkovskii infections among rural communities in Yemen. METHODS: In a community-based study, faecal samples were collected from 605 participants and examined by wet mount, formalin-ether sedimentation, trichrome staining and nested multiplex PCR techniques. Demographic, socio-economic and environmental information was collected using a pre-tested questionnaire. RESULTS: Overall, 324 (53.6%) of the samples were positive for Entamoeba cysts and/or trophozoites by microscopic examination. Molecular analysis revealed that 20.2%, 15.7% and 18.2% of the samples were positive for E. histolytica, E. dispar and E. moshkovskii, respectively. Multivariate analysis showed different sets of species-specific risk factors among these communities. Educational level was identified as the significant risk factor for E. histolytica; age and gender were the significant risk factors for E. moshkovskii; and sources of drinking water and consumption of unwashed vegetables were the significant risk factors for E. dispar. Moreover, living in coastal/foothill areas and presence of other infected family members were risk factors for both E. histolytica and E. moshkovskii infections. CONCLUSION: The study reveals that Entamoeba spp. infection is highly prevalent among rural communities in Yemen, with E. histolytica, E. dispar and E. moshkovskii differentiated for the first time. Identifying and treating infected family members, providing health education pertinent to good personal and food hygiene practices and providing clean drinking water should be considered in developing a strategy to control intestinal parasitic infections in these communities, particularly in the coastal/foothill areas of the country.
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Entamoeba/crecimiento & desarrollo , Entamebiasis/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Niño , Preescolar , Agua Potable/parasitología , Entamoeba/genética , Entamoeba histolytica/genética , Entamebiasis/epidemiología , Entamebiasis/parasitología , Heces/parasitología , Femenino , Humanos , Higiene , Lactante , Masculino , Persona de Mediana Edad , Epidemiología Molecular , Reacción en Cadena de la Polimerasa/métodos , Factores de Riesgo , Factores Socioeconómicos , Yemen , Adulto JovenRESUMEN
INTRODUCTION: Febrile neutropenia is a common complication of chemotherapy treatment of malignant hematological diseases. However, there is insufficient information regarding the infectious complications of febrile neutropenia in our country. Objective. We will evaluate the microbial characteristics of bacterial and fungal isolates and the clinical outcome of patients with febrile neutropenia who received medical attention at an oncological reference center in Colombia. MATERIALS AND METHODS: A prospective case series included patients with histologically confirmed oncological disease, who were admitted because of febrile neutropenia or presented with febrile neutropenia during hospitalization. Patients with benign hematological diseases were excluded. Demographic, microbiological, and clinical features as well as treatment and outcome information from patients with febrile neutropenia were obtained. We performed univariate and multivariate analyses, with mortality defined as the outcome. RESULTS: One hundred and thirty episodes of febrile neutropenia were identified in 104 patients. The mean patient age was 19, and 53% of the patients were male. Approximately 86% of the episodes occurred in patients with hematological disorders. An infectious site was identified in 65% of patients; 41% and 24% of the febrile neutropenia pateints´ episodes exhibited a localized infectious focus and developed bloodstream infections, respectively. The majority of infections were found in blood, urine, gastrointestinal tract, and soft tissue. Distribution analysis of microbiological isolates revealed 46.4% Gram-negative bacilli, 38.4% Gram-positive cocci, 8% fungi, and 7.1% parasites; there was a 7.7% mortality rate. Appropriate empirical antimicrobial therapy was a protection-related factor in multivariate analyses (OR= 0.17; 0.034 - 0.9 95% CI; p= 0.037). CONCLUSIONS: The mortality rate was relatively low and comparable to the rate reported by developed countries. Inappropriate empirical antimicrobial therapy was the main factor associated with mortality.
Asunto(s)
Infecciones Bacterianas/etiología , Instituciones Oncológicas , Neutropenia Febril Inducida por Quimioterapia/epidemiología , Prescripción Inadecuada/estadística & datos numéricos , Micosis/etiología , Adolescente , Adulto , Anciano , Antibacterianos/uso terapéutico , Profilaxis Antibiótica/estadística & datos numéricos , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/epidemiología , Infecciones Bacterianas/microbiología , Neutropenia Febril Inducida por Quimioterapia/complicaciones , Niño , Preescolar , Colombia/epidemiología , Infección Hospitalaria/epidemiología , Infección Hospitalaria/etiología , Entamebiasis/tratamiento farmacológico , Entamebiasis/epidemiología , Entamebiasis/etiología , Entamebiasis/parasitología , Femenino , Mortalidad Hospitalaria , Humanos , Lactante , Masculino , Persona de Mediana Edad , Micosis/tratamiento farmacológico , Micosis/epidemiología , Micosis/microbiología , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Especificidad de Órganos , Estudios Prospectivos , Recurrencia , Adulto JovenRESUMEN
Introduction. Febrile neutropenia is a common complication of chemotherapy treatment of malignant hematological diseases. However, there is insufficient information regarding the infectious complications of febrile neutropenia in our country. Objective. We will evaluate the microbial characteristics of bacterial and fungal isolates and the clinical outcome of patients with febrile neutropenia who received medical attention at an oncological reference center in Colombia. Materials and methods. A prospective case series included patients with histologically confirmed oncological disease, who were admitted because of febrile neutropenia or presented with febrile neutropenia during hospitalization. Patients with benign hematological diseases were excluded. Demographic, microbiological, and clinical features as well as treatment and outcome information from patients with febrile neutropenia were obtained. We performed univariate and multivariate analyses, with mortality defined as the outcome. Results. One hundred and thirty episodes of febrile neutropenia were identified in 104 patients. The mean patient age was 19, and 53% of the patients were male. Approximately 86% of the episodes occurred in patients with hematological disorders. An infectious site was identified in 65% of patients; 41% and 24% of the febrile neutropenia pateints´ episodes exhibited a localized infectious focus and developed bloodstream infections, respectively. The majority of infections were found in blood, urine, gastrointestinal tract, and soft tissue. Distribution analysis of microbiological isolates revealed 46.4% Gram-negative bacilli, 38.4% Gram-positive cocci, 8% fungi, and 7.1% parasites; there was a 7.7% mortality rate. Appropriate empirical antimicrobial therapy was a protection-related factor in multivariate analyses (OR= 0.17; 0.034 - 0.9 95% CI; p= 0.037). Conclusions. The mortality rate was relatively low and comparable to the rate reported by developed countries. Inappropriate empirical antimicrobial therapy was the main factor associated with mortality.
Introducción. La neutropenia febril es una complicación frecuente de la quimioterapia para las neoplasias hematológicas. Se dispone de escasa información de sus complicaciones infecciosas en nuestro medio. Objetivo. Evaluar las características clínicas y microbiológicas de pacientes con neutropenia febril, así como su resultado clínico en una institución de referencia oncológica en Colombia. Materiales y métodos. Se conformó prospectivamente una serie de casos con pacientes con enfermedad oncológica confirmada, que consultaron o presentaron neutropenia febril durante la hospitalización. Se excluyeron aquellos con enfermedad hematológica benigna. Se recolectaron datos sobre variables demográficas, microbiológicas, clínicas, de tratamiento y de resultado de los pacientes. Se llevaron a cabo un análisis univariado y uno multivariado, con la mortalidad como resultado. Resultados. Se identificaron 130 episodios de neutropenia febril en 104 pacientes, con una edad media de 19 años y 53 % masculinos. El 86 % de los episodios ocurrieron en pacientes con alteraciones hematológicas. Se demostró infección en 65 % de los casos: 41 % con un foco infeccioso localizado y 27,7 % con bacteriemia. Los principales focos infecciosos se localizaron en el torrente sanguíneo, el aparato urinario, el sistema gastrointestinal, la piel y los tejidos blandos. De los aislamientos microbiológicos, 46,4 % fueron bacilos Gram negativos, 38,4 %, cocos Gram positivos, 9 %, hongos y, 7,1%, parásitos. La mortalidad global fue de 7,7 %. En el análisis multivariado la utilización de un tratamiento empírico apropiado se correlacionó con una menor mortalidad, de forma independiente (OR=0,17; IC 95% 0,034-0,9; p=0,037). Conclusiones. La tasa de mortalidad fue relativamente baja y fue comparable con lo reportado en países desarrollados. El tratamiento antimicrobiano inapropiado fue el principal factor asociado con mortalidad.
Asunto(s)
Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Adulto Joven , Infecciones Bacterianas/etiología , Instituciones Oncológicas , Neutropenia Febril Inducida por Quimioterapia/epidemiología , Prescripción Inadecuada/estadística & datos numéricos , Micosis/etiología , Antibacterianos/uso terapéutico , Profilaxis Antibiótica , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/epidemiología , Infecciones Bacterianas/microbiología , Neutropenia Febril Inducida por Quimioterapia/complicaciones , Colombia/epidemiología , Infección Hospitalaria/epidemiología , Infección Hospitalaria/etiología , Entamebiasis/tratamiento farmacológico , Entamebiasis/epidemiología , Entamebiasis/etiología , Entamebiasis/parasitología , Mortalidad Hospitalaria , Micosis/tratamiento farmacológico , Micosis/epidemiología , Micosis/microbiología , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Especificidad de Órganos , Estudios Prospectivos , RecurrenciaAsunto(s)
Antineoplásicos Hormonales/efectos adversos , Antineoplásicos Hormonales/uso terapéutico , Dexametasona/efectos adversos , Disentería Amebiana/etiología , Entamebiasis/etiología , Mieloma Múltiple/complicaciones , Mieloma Múltiple/tratamiento farmacológico , Dexametasona/uso terapéutico , Disentería Amebiana/microbiología , Disentería Amebiana/patología , Entamoeba histolytica/patogenicidad , Entamebiasis/microbiología , Entamebiasis/patología , Resultado Fatal , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/diagnósticoAsunto(s)
Entamebiasis/etiología , Hepatitis B/etiología , Homosexualidad Masculina , Sífilis Cutánea/etiología , Sexo Inseguro , Enfermedad Aguda , Antiinfecciosos/uso terapéutico , Antiprotozoarios/uso terapéutico , Antivirales/uso terapéutico , Colonoscopía , Entamebiasis/diagnóstico , Entamebiasis/tratamiento farmacológico , Entamebiasis/patología , Hemorragia Gastrointestinal/etiología , Hepatitis B/diagnóstico , Hepatitis B/tratamiento farmacológico , Hepatitis B/patología , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/inmunología , Humanos , Inmunoglobulina M/sangre , Ictericia/etiología , Lamivudine/uso terapéutico , Masculino , Metronidazol/uso terapéutico , Persona de Mediana Edad , Penicilinas/uso terapéutico , Recto , Serodiagnóstico de la Sífilis , Sífilis Cutánea/diagnóstico , Sífilis Cutánea/tratamiento farmacológico , Sífilis Cutánea/patologíaRESUMEN
BACKGROUND: Foot infections are a common reason for hospitalization and a cause of complications in patients with diabetes. The aim of this study was to determine the prevalence of microorganisms found on culture in complicated diabetic foot infections in hospitalized patients, and the sensitivity of the causative microorganisms to antimicrobial agents. METHODS: Between December 2001 and December 2005 in our department, 84 samples in 62 diabetic patients with moderate/severe infection were collected for microbiological study. RESULTS: At least one microorganism was isolated in 88% of samples. The most frequently isolated germ group was gram-positive bacteria (55% of the samples), with Staphylococcus aureus (33%) in the first position, followed by Pseudomonas aeruginosa (12%), Enterococcus spp. (9%), and Escherichia coli (8%). Culture for anaerobic microorganisms was only performed in half the samples; 25% were positive, and Peptostreptococcus spp. predominated. Among the multiresistant microorganisms, methicillin-resistant staphylococci aureus (MRSA) were the most common, accounting for 38% of the isolated strains of S. aureus, ie, 12% of all samples. As to the gram-negative microorganisms, nearly 30% of E. coli strains were resistant to amoxicillin/clavulanic acid and ciprofloxacin. CONCLUSION: Most of the cultures in our study were monomicrobial, with S. aureus being the most prevalent microorganism, followed by enterobacteria and P. aeruginosa. The main resistant microorganism in diabetic foot infections requiring hospitalization was methicillin-resistant golden staphylococcus, which was found in 12% of the series.
Asunto(s)
Antibacterianos/uso terapéutico , Pie Diabético/microbiología , Farmacorresistencia Bacteriana Múltiple , Infecciones por Bacterias Gramnegativas/microbiología , Infecciones por Bacterias Grampositivas/microbiología , Enfermedades Cutáneas Bacterianas/microbiología , Adulto , Anciano , Anciano de 80 o más Años , Amebicidas/farmacología , Amebicidas/uso terapéutico , Antibacterianos/farmacología , Técnicas Bacteriológicas , Pie Diabético/tratamiento farmacológico , Pie Diabético/epidemiología , Pie Diabético/parasitología , Resistencia a Medicamentos , Entamoeba/efectos de los fármacos , Entamoeba/aislamiento & purificación , Entamebiasis/tratamiento farmacológico , Entamebiasis/etiología , Entamebiasis/parasitología , Femenino , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/epidemiología , Infecciones por Bacterias Gramnegativas/etiología , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/epidemiología , Infecciones por Bacterias Grampositivas/etiología , Humanos , Masculino , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/epidemiología , Infecciones por Pseudomonas/etiología , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/aislamiento & purificación , Enfermedades Cutáneas Bacterianas/tratamiento farmacológico , Enfermedades Cutáneas Bacterianas/epidemiología , Enfermedades Cutáneas Bacterianas/etiología , España/epidemiología , Especificidad de la Especie , Infecciones Cutáneas Estafilocócicas/tratamiento farmacológico , Infecciones Cutáneas Estafilocócicas/epidemiología , Infecciones Cutáneas Estafilocócicas/etiología , Infecciones Cutáneas Estafilocócicas/microbiologíaRESUMEN
Medical records, for 2000 and 2001, of symptomatic amoebic patients who were treated at our hospitals in Tokyo, Yokohama and Osaka were studied retrospectively for the purpose of gathering epidemiological data on symptomatic Entamoeba histolytica infection. A total of 58 patients were treated. Fifty-five of them were male, and 96% of the male patients were Japanese. The mean age of patients was 44.9 years old, and 91% of patients contracted the disease in Japan. Fifty-six per cent of the male patients indicated that they were practising homosexuals, and 44% of the male patients denied these practices or left the question unanswered. The serum Treponema pallidum haemagglutination test was positive in 45% of the patients, and antibody to human immunodeficiency virus (HIV) was positive in 45%. Our study revealed that recent symptomatic E. histolytica infection almost exclusively afflicted middle-aged males in the big cities of Japan, that a majority of the patients were probably exposed to the causative organism during homosexual activity, and that an increasing number of patients will be co-infected with HIV.
Asunto(s)
Entamoeba histolytica , Entamebiasis/epidemiología , Salud Urbana/estadística & datos numéricos , Serodiagnóstico del SIDA , Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Infecciones Oportunistas Relacionadas con el SIDA/etiología , Infecciones Oportunistas Relacionadas con el SIDA/transmisión , Adolescente , Adulto , Distribución por Edad , Animales , Entamebiasis/diagnóstico , Entamebiasis/etiología , Entamebiasis/transmisión , Femenino , Pruebas de Hemaglutinación , Homosexualidad Masculina/estadística & datos numéricos , Hospitales Generales , Humanos , Incidencia , Japón/epidemiología , Masculino , Persona de Mediana Edad , Vigilancia de la Población , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Distribución por SexoRESUMEN
An unusual late complication to an orbital floor fracture is presented. Five years after trauma a now 22-year old man demonstrated an entamoeba infected cyst in the orbit.
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Quistes/parasitología , Entamoeba histolytica/aislamiento & purificación , Entamebiasis/etiología , Enfermedades Orbitales/parasitología , Fracturas Orbitales/complicaciones , Adulto , Animales , Quistes/cirugía , Drenaje/métodos , Entamebiasis/cirugía , Humanos , Imagen por Resonancia Magnética , Masculino , Órbita/lesiones , Enfermedades Orbitales/cirugía , Tomografía Computarizada por Rayos XRESUMEN
Amebiasis caused by Entamoeba histolytica at an institution for mentally retarded in Shizuoka Prefecture is reported. Five of the 50 patients showed E. histolytica cysts in their stools and 4 were positive serologically. The polymerase chain reaction and restriction fragment length polymorphism revealed that the isolates were pathogenic-type E. histolytica. Epidemiological analysis revealed that the amebic infection was caused by the abnormal behavior of mentally retarded patients. Administration of diloxanide furoate and metronidazole for cyst-carriers eliminated cysts from the stool and lowered the antibody titer.
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Entamebiasis/epidemiología , Discapacidad Intelectual/complicaciones , Adulto , Animales , Entamoeba histolytica/aislamiento & purificación , Entamebiasis/etiología , Entamebiasis/parasitología , Femenino , Humanos , Institucionalización , Japón/epidemiología , MasculinoRESUMEN
Advancements in our understanding of amebiasis have been rapid over the decade that I have followed this field. What was identified morphologically for years as Entamoeba histolytica has been redescribed with modern techniques as a complex of two species, the commensal parasite E. dispar and the pathogenic parasite E. histolytica that is the cause of colitis and liver abscess. Antigen detection tests are now available for the rapid detection in stool of the pathogenic species E. histolytica. New understandings of the importance of luminal as well as tissue-active antimebic medications in the treatment of invasive disease have been reached. The groundwork is being laid for an understanding of the protective immune responses to infection, and at the lab bench DNA transfection of the parasite has opened studies of pathogenesis to genetic analysis. While necessarily an incomplete sketch of the field, I have attempted here to highlight some recent and important developments of interest to clinicians and microbiologists.
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Entamebiasis , Animales , Antígenos de Protozoos/análisis , Secuencia de Bases , ADN Protozoario/análisis , Entamoeba/genética , Entamoeba/inmunología , Entamoeba/aislamiento & purificación , Entamoeba/fisiología , Entamebiasis/diagnóstico , Entamebiasis/etiología , Entamebiasis/terapia , Heces/parasitología , Humanos , Datos de Secuencia MolecularRESUMEN
The Entamoeba histolytica 27-kDa cysteine proteinases exhibit striking binding specificities for immobilized laminin over other components of the extracellular matrix, such as collagen and fibronectin. Inactivation of the proteinase with the active-site inhibitor L-trans-epoxysuccinyl-leucylamido(4-guanidino)butane abolishes laminin binding by the enzyme, and conversely, laminin inhibits cleavage of a fluorogenic dipeptide substrate of the amebic cysteine proteinase, suggesting that the substrate binding pocket of the enzyme is involved in the binding of laminin. The addition of laminin but not fibronectin or collagen to E. histolytica trophozoites significantly reduces amebic liver abscess formation in severe combined immunodeficient mice, further supporting the hypothesis that E. histolytica cysteine proteinases play an important role in amebic pathogenesis. The specific interaction of amebic proteinases with laminin may be exploited in designing new inhibitors of these enzymes.
Asunto(s)
Cisteína Endopeptidasas/metabolismo , Entamoeba histolytica/enzimología , Entamebiasis/etiología , Laminina/metabolismo , Secuencia de Aminoácidos , Animales , Entamoeba histolytica/patogenicidad , Leucina/análogos & derivados , Leucina/farmacología , Datos de Secuencia MolecularRESUMEN
We have successfully transfected Entamoeba histolytica trophozoites with constructs containing ferredoxin sequences fused to the reporter gene luciferase. We have determined the conditions and parameters necessary to maximise transient luciferase expression in our system. Our optimal construct gave values of 268 x 10(3) relative light units per second (RLU s-1) when assayed representing a stimulation of 18,000-fold over the control vector. Comparison of differing constructs allowed us to conclude that the 5' and 3' ferredoxin sequences are both necessary for optimal luciferase expression from our vectors. Transcriptional initiation occurs within the consensus sequence ATTCA in both construct and chromosomal ferredoxin promoters.
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Entamoeba histolytica/enzimología , Entamoeba histolytica/genética , Ferredoxinas/genética , Genes Protozoarios , Luciferasas/genética , Animales , Secuencia de Bases , Cartilla de ADN/genética , ADN Protozoario/genética , Entamoeba histolytica/patogenicidad , Entamebiasis/etiología , Expresión Génica , Genes Reguladores , Genes Reporteros , Vectores Genéticos , Humanos , Datos de Secuencia Molecular , Plásmidos/genética , Transfección , Virulencia/genéticaRESUMEN
Genital amebiasis is a rare complication of infection with Entamoeba histolytica, even in areas where the pathogen is endemic. We describe a patient who apparently contracted intestinal amebiasis on a trip to Mexico and who presented with ulcerative vulvovaginitis 2 months later. Her condition rapidly progressed to severe necrotizing vulvovaginitis that required a radical vulvectomy. Histopathologic examination of the surgical specimen revealed the presence of E. histolytica trophozoites. The patient recovered after surgery and antiamebic therapy. We review the epidemiology and pathogenesis of genital amebiasis as well as therapy for this rare infection.