RESUMO
The causative agent of human Q fever, Coxiella burnetii, is highly adapted to infect alveolar macrophages by inhibiting a range of host responses to infection. Despite the clinical and biological importance of this pathogen, the challenges related to genetic manipulation of both C. burnetii and macrophages have limited our knowledge of the mechanisms by which C. burnetii subverts macrophages functions. Here, we used the related bacterium Legionella pneumophila to perform a comprehensive screen of C. burnetii effectors that interfere with innate immune responses and host death using the greater wax moth Galleria mellonella and mouse bone marrow-derived macrophages. We identified MceF (Mitochondrial Coxiella effector protein F), a C. burnetii effector protein that localizes to mitochondria and contributes to host cell survival. MceF was shown to enhance mitochondrial function, delay membrane damage, and decrease mitochondrial ROS production induced by rotenone. Mechanistically, MceF recruits the host antioxidant protein Glutathione Peroxidase 4 (GPX4) to the mitochondria. The protective functions of MceF were absent in primary macrophages lacking GPX4, while overexpression of MceF in human cells protected against oxidative stress-induced cell death. C. burnetii lacking MceF was replication competent in mammalian cells but induced higher mortality in G. mellonella, indicating that MceF modulates the host response to infection. This study reveals an important C. burnetii strategy to subvert macrophage cell death and host immunity and demonstrates that modulation of the host antioxidant system is a viable strategy to promote the success of intracellular bacteria.
Assuntos
Antioxidantes , Coxiella , Humanos , Animais , Camundongos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Estresse Oxidativo , Morte Celular , MamíferosRESUMO
El aislamiento y detección de Legionella pneumophila en agua potable puede ser un proceso difícil, debido a que algunas de las técnicas existentes no recuperan la cantidad establecida por normas internacionales y al ser un microorganismo exigente, se requiere de medios especiales para su crecimiento. El objetivo del estudio fue validar un método de concentración por medio de la implementación del equipo Celltrazone® para lograr la recuperación en agar BCYE, utilizando muestras de agua potable con diferentes concentraciones de la bacteria. Para lograr este objetivo, se ensayaron tres tipos de tratamiento para el filtro obtenido después de la filtración por el equipo Celltrazone®, el vortex, sonicado y agitación, sin embargo, al no aplicar ningún procedimiento al filtro y realizar su siembra directa se obtuvieron los mejores resultados. El análisis estadístico demostró que con el método seleccionado se puede concentrar hasta 1x102 UFC, se alcanzó una sensibilidad del 100%, una especificidad del 80% y un valor de exactitud del 87,5%. El método de filtración de membrana utilizando el equipo Celltrazone® permitió aumentar la concentración de L. pneumophila en agua potable, cumpliendo con los intervalos normalizados por ISO y la OMS, por lo tanto, el método es apto para su aplicación asegurando resultados confiables.
The isolation and detection of Legionella pneumophila in drinking water can be a difficult process due to the fact that some of the existing techniques do not recover the amount established by international standards and, as it is a demanding microorganism, special media are required for its isolation and growth. The objective of this study was to validate a concentration method through the implementation of the Celltrazone® equipment to achieve recovery in BCYE agar, using drinking water samples with different concentrations of the bacteria. To achieve this objective, three types of treatment were tested for the filter obtained after filtration by the Celltrazone® equipment, vortex, sonication and agitation; however, better results were obtained without applying any procedure to the filter and performing direct seeding. Statistical analysis showed that up to 1x102 CFU can be concentrated with the selected method, a sensitivity of 100%, a specificity of 80% and an accuracy value of 87.5% were achieved. The membrane filtration method using the Celltrazone® equipment allowed to increase the concentration of L. pneumophila in drinking water, complying with the normalized intervals by ISO and WHO; therefore, the method is suitable for its application, ensuring reliable results.
Assuntos
HumanosRESUMO
Resumen La inmunidad conferida luego de una primera infección por SARS-CoV-2 y el riesgo consiguiente de infección persistente o reinfección no están completamente dilucidados. Existen reportes internacionales de casos de reinfección, incluyendo el primer caso publicado en Sudamérica. Por otra parte, las comunicaciones de casos de coinfecciones han ido en aumento, incluyendo las asociadas a Legionella pneumophila . Presentamos el caso de un varón de 47 años de edad, personal de salud, que luego de cuatro meses de una primera infección por SARS-CoV-2, presenta una neumonía grave, certificándose una nueva infección por SARS-CoV-2 y una coinfección por L. pneumophila mediante detección de antígeno urinario. Fue tratado en UCI, requiriendo ventilación mecánica, dexametaxona y moxifloxacino, con buena respuesta clínica. Actualmente se encuentra en rehabilitación respiratoria y motora.
Abstract The immunity conferred after a first SARS-CoV-2 infection and the consequent risk of persistent infection or reinfection are not fully elucidated. There are reports both in Europe and in North America of reinfection cases, recently highlighting the first case published in South America. On the other hand, reports of co-infections have been increasing, including those associated with Legionella pneumophila . We present the case of a 47-year-old male, health personnel who, after four months of a first SARS-CoV-2 infection, suffers a severe pneumonia certifying a new SARS-CoV-2 infection and a L. pneumophila co-infection by urinary antigen detection. He was treated in the ICU, requiring mechanical ventilation, dexamethasone, and moxifloxacin, with a good response. He is currently in respiratory and motor rehabilitation.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Doença dos Legionários/complicações , Coinfecção , COVID-19/complicações , Legionella pneumophila , Reinfecção , SARS-CoV-2RESUMO
La enfermedad del Legionario es causada por bacterias pertenecientes al género Legionella, siendo la especie pneumophila el principal agente etiológico de esta patología. Esta bacteria se describió por primera vez en 1977 como causa de un brote de neumonía grave registrado en 1976 en un centro de convenciones en los Estados Unidos de América. La enfermedad se presenta como una neumonía atípica, responsable del 1 al 15 % de los casos de neumonías adquiridas en la comunidad (NAC), del 5 al 10% de neumonías del adulto y del 1% en menores de 15 años. Los miembros de la familia Legionellaceae son bacilos aeróbicos gramnegativos que crecen lentamente y se encuentran ampliamente distribuidos en cuerpos de agua. La forma más común de transmisión de Legionella spp es la inhalación de aerosoles contaminados generados a partir de fuentes de agua artificiales. Se asocian con la aparición de brotes esporádicos y epidémicos en la comunidad y en infecciones nosocomiales. Las especies pertenecientes al género Legionella se consideran patógenos emergentes transmitidos por el agua. El objetivo de este trabajo es realizar una revisión sobre las manifestaciones y presentaciones clínicas de la infección causada por L. pneumophila, en virtud de que es considerado mundialmente un patógeno emergente y por existir evidencias de su presencia en sistemas de almacenamiento de agua tratada en la región nordeste de la República Argentina, razón primordial para alertar y actualizar conocimientos al respecto
Legionnaires' disease is caused by bacteria belonging to the genus Legionella, being the pneumophila specie the main etiological agent of this pathology. This bacterium was first described in 1977 as the cause of a severe pneumonia outbreak in 1976 at a convention center in the United States of America. The disease presents as an atypical pneumonia, responsible for 1% to 15% of cases of community-acquired pneumonia (CAP), 5% to 10% of pneumonia in adults and 1% in children under 15 years of age. Members of the Legionellaceae family are aerobic, gram-negative rods that grow slowly and are widely distributed in water bodies. The most common way of transmission of Legionella spp is the inhalation of contaminated aerosols generated from artificial water sources. They are associated with the appearance of sporadic and epidemic outbreaks in the community and in nosocomial infections. Species belonging to the genus Legionella are considered emerging waterborne pathogens.The aim of this work is to carry out a review on the manifestations and clinical presentations of the infection caused by L. pneumophila, due to that it is considered an emerging pathogen worldwide and because there is evidence of its presence in storage systems of treated water in the Northeast region of the Argentine Republic, primary reason to alert and update knowledge in this regard.
Assuntos
Humanos , Doença dos Legionários/prevenção & controle , Doença dos Legionários/transmissão , Armazenamento de Água , Crescimento Bacteriano/prevenção & controleRESUMO
ABSTRACT Objective The goal of this study is to determine the risk of exposure to Legionella pneumophila in hotel golf courses located in the province of Malaga (Spain). Method Spray irrigation systems were analyzed as sources for spreading the Legionella bacterium. Spanish legislation requires that irrigation systems be monitored for their water quality as well as for reasons related to health and hygiene. Based on an observational study and non-parametric tests (Goodman-Kruskal Tau and uncertainty coefficient), this study states the regulatory enforcement among the systems and contributed to announce Legionella prevention. The quality criteria for recycled water, waste water treatment plant and well water were analyzed in relationship to the hotels' categories. Results Deficiencies were found in the preventive maintenance of irrigation systems, but no relationship exists between the type of water and the risk detected. Conclusions The study suggests that aerosolized water used in golf course watering systems could pose risk to the population by exposing them to Legionella.
RESUMEN Objetivo El propósito de este trabajo es determinar el riesgo de exposición a Legionella pneumophila en campos de golf de hoteles ubicados en la provincia de Málaga (España). Método Se realizó un estudio de los sistemas de riego por aspersión como fuentes de dispersión de la bacteria Legionella. El análisis de las condiciones higiénico-sanitarias de las instalaciones y la calidad del agua es una actividad de obligado cumplimiento contemplada en la legislación sanitaria española. Mediante un estudio observacional y el empleo de pruebas no paramétricas (Tau de Goodman-Kruskal y coeficiente de incertidumbre) se expresó el cumplimiento de la reglamentación en los sistemas estudiados y la prevención de Legionella. Los criterios de calidad para el agua reciclada, procedente de la estación depuradora de agua residual y de pozo, fueron analizados en relación con la categoría de los hoteles. Resultados Se encontraron deficiencias en el mantenimiento preventivo de los sistemas de riego, pero no hubo relación entre el tipo de agua y el riesgo identificado. Conclusiones El estudio sugiere que el agua aerosolizada proveniente de los sistemas de riego de los campos de golf presenta un riesgo de infección por Legionella para la población expuesta.
RESUMO
INTRODUCCIÓN El género Legionella comprende especies ampliamente distribuidas en ambientes acuáticos. Son capaces de sobrevivir en un amplio intervalo de condiciones físico-químicas y colonizar los sistemas de distribución y almacenamiento del agua potable. L. pneumophila es el principal patógeno trasmitido por el agua, que produce el 90% de los casos de legionelosis. OBJETIVOS Detectar la presencia de Legionella pneumophila en los depósitos domiciliarios de agua potable de la ciudad de Resistencia, Chaco. MÉTODOS El muestreo fue no probabilístico por conveniencia. Se estudiaron 30 muestras de agua tomadas en diferentes puntos de la ciudad. La detección de Legionella en las muestras se realizó por cultivo según lo establecido en la norma ISO 11731 1998. Los aislamientos obtenidos por cultivo e identificados como Legionella spp. se estudiaron con la técnica de PCR en tiempo real con colorante intercalante (Syber Green), qPCR. Las secuencias diana utilizadas para la identificación de Legionella correspondieron a fragmentos conservados del gen 23S rRNA, para la confirmación del género, y el gen mip específico para la especie L. pneumophila. RESULTADOS En 11 (36,7%) de las 30 muestras estudiadas se recuperaron cepas de Legionella spp. Mediante qPCR se confirmó la presencia de L. pneumophila en las 11 muestras positivas por cultivo. Además, 3 de estas muestras (10%) también resultaron positivas para otra/s especie/s del género Legionella. DISCUSIÓN El presente trabajo demostró la presencia de L. pneumophila y otras especies de Legionella en los reservorios domiciliarios de agua potable, por lo que la vigilancia de este microorganismo en el agua de consumo humano representa el primer paso en pos de abordar el control de su diseminación hacia huéspedes susceptibles.
Assuntos
Água Potável , Legionella pneumophilaRESUMO
Cellular responses to stress can be defined by the overwhelming number of changes that cells go through upon contact with and stressful conditions such as infection and modifications in nutritional status. One of the main cellular responses to stress is autophagy. Much progress has been made in the understanding of the mechanisms involved in the induction of autophagy during infection by intracellular bacteria. This review aims to discuss recent findings on the role of autophagy as a cellular response to intracellular bacterial pathogens such as, Streptococcus pyogenes, Mycobacterium tuberculosis, Shigella flexneri, Salmonella typhimurium, Listeria monocytogenes, and Legionella pneumophila, how the autophagic machinery senses these bacteria directly or indirectly (through the detection of bacteria-induced nutritional stress), and how some of these bacterial pathogens manage to escape from autophagy.
Assuntos
Autofagia , Infecções Bacterianas/microbiologia , Fenômenos Fisiológicos Bacterianos , Interações Hospedeiro-Patógeno , Espaço Intracelular/microbiologia , Proteínas Quinases Ativadas por AMP/metabolismo , Aminoácidos/metabolismo , Animais , Autofagossomos/imunologia , Autofagossomos/metabolismo , Autofagossomos/microbiologia , Autofagia/imunologia , Infecções Bacterianas/imunologia , Infecções Bacterianas/metabolismo , Fenômenos Fisiológicos Bacterianos/imunologia , Transporte Biológico , Biomarcadores , Interações Hospedeiro-Patógeno/imunologia , Humanos , Espaço Intracelular/imunologia , Espaço Intracelular/metabolismo , Transdução de SinaisRESUMO
Nine Legionella pneumophila strains isolated from cooling towers and a standard strain (L. pneumophila serogroup 1, ATCC 33152, Philadelphia 1) were analyzed and compared in terms of motility, flagella structure, ability to form biofilms, enzymatic activities (hemolysin, nucleases, protease, phospholipase A, phospholipase C, acid phosphatase, alkaline phosphatase and lipase), hemagglutination capabilities, and pathogenicity in various host cells (Acanthamoeba castellanii ATCC 30234, mouse peritoneal macrophages and human peripheral monocytes). All the isolates of bacteria appeared to be motile and polar-flagellated and possessed the type-IV fimbria. Upon the evaluation of virulence factors, isolate 4 was found to be the most pathogenic strain, while 6 out of the 9 isolates (the isolates 1, 2, 3, 4, 5, and 7) were more virulent than the ATCC 33152 strain. The different bacterial strains exhibited differences in properties such as adhesion, penetration and reproduction in the hosts, and preferred host type. To our knowledge, this is the first study to compare the virulence of environmental L. pneumophila strains isolated in Turkey, and it provides important information relevant for understanding the epidemiology of L. pneumophila.(AU)
Assuntos
Legionella pneumophila/patogenicidade , Virulência , Estudos Epidemiológicos , TurquiaRESUMO
ABSTRACT Nine Legionella pneumophila strains isolated from cooling towers and a standard strain (L. pneumophila serogroup 1, ATCC 33152, Philadelphia 1) were analyzed and compared in terms of motility, flagella structure, ability to form biofilms, enzymatic activities (hemolysin, nucleases, protease, phospholipase A, phospholipase C, acid phosphatase, alkaline phosphatase and lipase), hemagglutination capabilities, and pathogenicity in various host cells (Acanthamoeba castellanii ATCC 30234, mouse peritoneal macrophages and human peripheral monocytes). All the isolates of bacteria appeared to be motile and polar-flagellated and possessed the type-IV fimbria. Upon the evaluation of virulence factors, isolate 4 was found to be the most pathogenic strain, while 6 out of the 9 isolates (the isolates 1, 2, 3, 4, 5, and 7) were more virulent than the ATCC 33152 strain. The different bacterial strains exhibited differences in properties such as adhesion, penetration and reproduction in the hosts, and preferred host type. To our knowledge, this is the first study to compare the virulence of environmental L. pneumophila strains isolated in Turkey, and it provides important information relevant for understanding the epidemiology of L. pneumophila.
Assuntos
Humanos , Animais , Feminino , Camundongos , Proteínas de Bactérias/metabolismo , Legionella pneumophila/metabolismo , Fatores de Virulência/metabolismo , Proteínas de Bactérias/genética , Turquia/epidemiologia , Doença dos Legionários/microbiologia , Legionella pneumophila/isolamento & purificação , Legionella pneumophila/genética , Fatores de Virulência/genética , Microbiologia Ambiental , Macrófagos/microbiologia , Camundongos Endogâmicos BALB CRESUMO
Nine Legionella pneumophila strains isolated from cooling towers and a standard strain (L. pneumophila serogroup 1, ATCC 33152, Philadelphia 1) were analyzed and compared in terms of motility, flagella structure, ability to form biofilms, enzymatic activities (hemolysin, nucleases, protease, phospholipase A, phospholipase C, acid phosphatase, alkaline phosphatase and lipase), hemagglutination capabilities, and pathogenicity in various host cells (Acanthamoeba castellanii ATCC 30234, mouse peritoneal macrophages and human peripheral monocytes). All the isolates of bacteria appeared to be motile and polar-flagellated and possessed the type-IV fimbria. Upon the evaluation of virulence factors, isolate 4 was found to be the most pathogenic strain, while 6 out of the 9 isolates (the isolates 1, 2, 3, 4, 5, and 7) were more virulent than the ATCC 33152 strain. The different bacterial strains exhibited differences in properties such as adhesion, penetration and reproduction in the hosts, and preferred host type. To our knowledge, this is the first study to compare the virulence of environmental L. pneumophila strains isolated in Turkey, and it provides important information relevant for understanding the epidemiology of L. pneumophila.
Assuntos
Proteínas de Bactérias/metabolismo , Legionella pneumophila/metabolismo , Fatores de Virulência/metabolismo , Animais , Proteínas de Bactérias/genética , Microbiologia Ambiental , Feminino , Humanos , Legionella pneumophila/genética , Legionella pneumophila/isolamento & purificação , Doença dos Legionários/microbiologia , Macrófagos/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Turquia/epidemiologia , Fatores de Virulência/genéticaRESUMO
Inflammasomes are multimeric protein complexes that initiate inflammatory cascades. Their activation is a hallmark of many infectious or inflammatory diseases. Their composition and activity are specified by proinflammatory stimuli. For example, the NLRP3 inflammasome is activated in response to cell damage and K+ efflux, whereas the AIM2 inflammasome is activated in response to cytosolic DNA. We used Legionella pneumophila, an intracellular bacterial pathogen that activates multiple inflammasomes, to elucidate the molecular mechanisms regulating inflammasome activation during infection. Upon infection, the AIM2 inflammasome engaged caspase-1 to induce pore formation in the cell membrane, which then caused K+-efflux-mediated activation of NLRP3. Thus, the AIM2 inflammasome amplifies signals of infection, triggering noncanonical activation of NLRP3. During infection, AIM2 and caspase-11 induced membrane damage, which was sufficient and essential for activating the NLRP3 inflammasome. Our data reveal that different inflammasomes regulate one another's activity to ensure an effective immune response to infection.
Assuntos
Caspase 1/metabolismo , Proteínas de Ligação a DNA/metabolismo , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Animais , Caspase 1/genética , Caspases/metabolismo , Caspases Iniciadoras , Proteínas de Ligação a DNA/genética , Feminino , Flagelina/genética , Flagelina/metabolismo , Inflamassomos/genética , Inflamassomos/imunologia , Legionella pneumophila/imunologia , Legionella pneumophila/patogenicidade , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Potássio/metabolismoRESUMO
The Piscirickettsia salmonis genome was screened to evaluate potential flagella-related open reading frames, as well as their genomic organization and eventual expression. A complete and organized set of flagellar genes was found for P. salmonis, although no structural flagellum has ever been reported for this bacterium. To gain further understanding, the hierarchical flagellar cascade described for Legionella pneumophila was used as a reference model for putative analysis in P. salmonis. Specifically, 5 of the most relevant genes from this cascade were chosen, including 3 regulatory genes (fleQ, triggers the cascade; fliA, regulates the σ28-coding gene; and rpoN, an RNA polymerase-dependent gene) and 2 terminal structural genes (flaA and flaB, flagellin and a flagellin-like protein, respectively). Kinetic experiments evaluated gene expressions over time, with P. salmonis assessed in 2 liquid, cell-free media and during infection of the SHK-1 fish cell line. Under all conditions, the 5 target genes were primarily expressed during early growth/infection and were differentially expressed when bacteria encountered environmental stress (i.e. a high-salt concentration). Intriguingly, the flagellin monomer was fully expressed under all growth conditions and was located near the bacterial membrane. While no structural flagellum was detected under any condition, the recombinant flagellin monomer induced a proinflammatory response in SHK-1 cells, suggesting a possible immunomodulatory function. The potential implications of these observations are discussed in the context of P. salmonis biology and pathogenic potential.
Assuntos
Flagelina/metabolismo , Regulação da Expressão Gênica/fisiologia , Piscirickettsia/fisiologia , Sequência de Aminoácidos , Animais , Western Blotting , Linhagem Celular , DNA Complementar/genética , Flagelina/genética , Rim Cefálico/citologia , Cinética , Microscopia Confocal , Piscirickettsia/genética , Transporte Proteico , RNA Bacteriano/genética , SalmonidaeRESUMO
Introduction: Legionellosis is a multisystem bacterial disease, which causes pneumonia with high mortality in patients with comorbidity and admitted in intensive care units (ICU). Objective: Determine predictors of mortality or ICU admission. Methods: Retrospective follow-up of patients diagnosed with Legionella pneumophila pneumonia in Complexo Hospitalario Universitario de A Coruña. Period 2000-2013 (n = 240). Analysis of multivariate logistic regression was performed. Results: Mean age was 57.2 ± 15.4 years old, 88.3% were male. Average score of comorbidity (Charlson score) was 2.3 ± 2.3. There was a clear seasonal variation. Predominant symptoms were fever (92.5%), dry cough (38.1%) and dyspnea (33.9%). Creatinine clearance was lower than 60 mL/min/1.73 m² in 29.7% and sodium < 135 mEq/l in 58.3%. Admission to ICU rate was 16.3% and 10.8% needs mechanical ventilation. Inhospital mortality rate was 4.6%, rising to 23.1% in patients admitted to ICU. Variables associated to predict ICU admission were age (OR = 0.96), liver disease (OR = 7.13), dyspnea (OR = 4.33), delirium (OR = 5.86) and high levels of lactatedehydrogenase (OR = 1.002). Variables associated with inhospital mortality were Charlson index (OR = 1.70), mechanical ventilation (OR = 31.44) and high levels of lactatedehydrogenase (OR = 1.002). Discussion: Younger patients with liver disease, dyspnea and confusion are more likely to be admitted to ICU. Comorbidity, mechanical ventilation and elevated LDH levels are associated with higher mortality rate.
Introducción: La legionelosis es una enfermedad bacteriana multisistémica, causante de neumonías con mortalidad elevada en pacientes con comorbilidad e ingresos en Unidad de Cuidados Intensivos (UCI). Objetivo: Determinar factores pronósticos de mortalidad o ingreso en UCI. Material y Métodos: Estudio de seguimiento retrospectivo de pacientes diagnosticados de neumonía por Legionella pneumophila en Complexo Hospitalario Universitario de A Coruña (España). Período 2000-2013 (n = 240), con análisis de regresión logística multivariada. Resultados: La edad media fue 57,2 ± 15,4 años, 88,3% fueron hombres. La puntuación media de comorbilidad (score Charlson) fue 2,3 ± 2,3. Existe clara estacionalidad. La clínica predominante fue fiebre (92,5%), tos seca (38,1%) y disnea (33,9%). El 29,7% presentó aclaramiento de creatinina < 60 mL/min/1,73 m² y el 58,3% sodio < 135 mEq/l. Un 16,3% ingresó en UCI, precisando ventilación mecánica invasiva el 10,8%. La mortalidad global fue 4,6% y de 23,1% en ingresados en UCI. Variables asociadas para predecir ingreso en UCI fueron menor edad (OR = 0,96), hepatopatía (OR = 7,13), disnea (OR = 4,33), síndrome confusional (OR = 5,86) y lactato deshidrogenasa elevada (OR = 1,002). Las variables asociadas a mortalidad intrahospitalaria fueron índice de Charlson (OR = 1,70), ventilación mecánica invasiva (OR = 31,44) y cifras elevadas de lactato deshidrogenasa (OR = 1,002). Discusión: Pacientes jóvenes, con hepatopatía, disnea o confusión tienen más probabilidad de ingresar en UCI. Comorbilidad, ventilación mecánica y lactato deshidrogenasa elevada se asocian a mortalidad.
Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hospitalização , Legionella pneumophila , Doença dos Legionários/diagnóstico , Pneumonia Bacteriana/microbiologia , Fatores Etários , Comorbidade , Creatinina/metabolismo , Delírio/epidemiologia , Dispneia/epidemiologia , Mortalidade Hospitalar , Hospitalização/estatística & dados numéricos , Unidades de Terapia Intensiva/estatística & dados numéricos , L-Lactato Desidrogenase/sangue , Modelos Logísticos , Doença dos Legionários/mortalidade , Hepatopatias/epidemiologia , Prognóstico , Pneumonia Bacteriana/mortalidade , Estudos Retrospectivos , Estações do Ano , Espanha/epidemiologiaRESUMO
Legionella pneumophila, the etiological agent of Legionnaires' disease, triggers activation of multiple innate immune pathways that lead to the restriction of bacterial replication in vivo. Despite the critical role for MyD88 in infection clearance, the receptors and mechanisms responsible for MyD88-mediated pulmonary bacterial clearance are still unclear. Here, we used flagellin mutants of L. pneumophila, which bypass the NAIP5/NLRC4-mediated restriction of bacterial replication, to assess the receptors involved in MyD88-mediated pulmonary bacterial clearance. By systematically comparing pulmonary clearance of L. pneumophila in C57BL/6 MyD88(-/-), TLR2(-/-), TLR3(-/-), TLR4(-/-), TLR9(-/-), IL-1R(-/-), and IL-18(-/-) mice, we found that, while the knockout of a single Toll-like receptor or interleukin 18 resulted only in minor impairment of bacterial clearance, deficiency in the interleukin 1 (IL-1) receptor led to a significant impairment. IL-1/MyD88-mediated pulmonary bacterial clearance occurs via processes involving the recruitment of neutrophils. Collectively, our data contribute to the understanding of the effector mechanisms involved in MyD88-mediated pulmonary bacterial clearance.
Assuntos
Legionella pneumophila/imunologia , Doença dos Legionários/imunologia , Pulmão/imunologia , Fator 88 de Diferenciação Mieloide/metabolismo , Infiltração de Neutrófilos , Receptores de Interleucina-1/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Masculino , Camundongos Endogâmicos C57BL , Camundongos KnockoutRESUMO
Os antagonistas do fator de necrose tumoral (anti-TNF) têm sido utilizados com sucesso em várias doenças inflamatórias crônicas, como artrite reumatoide (AR), mas alguns estudos observaram a ocorrência de infecções por patógenos intracelulares em pacientes medicados com anti-TNF. Relatamos um caso de paciente mulher com diagnóstico prévio de AR durante 16 anos e que estava sendo medicada com várias drogas antirreumáticas modificadoras de doença (DARMDs), tendo como resultado o insucesso terapêutico, sendo em seguida tratada com infliximab. Depois de transcorridos 15 dias da segunda dose, a paciente foi acome- tida por dor torácica ventilatório-dependente, tosse seca e dispneia. Foi hospitalizada, e o diagnóstico de pneumonia por Legionella pneumophila foi confirmado pela presença do antí- geno de Legionella na urina. TNF é uma citocina inflamatória que também promove inibição do crescimento bacteriano de patógenos intracelulares, e sua inibição parece aumentar a sensibilidade a essas infecções em alguns pacientes.
The antagonists of tumour necrosis factor (anti-TNF) have been successfully used in several chronic inflammatory diseases such as Rheumatoid Arthritis (RA), but some studies have observed the development of infections by intracellular pathogens in patients using anti-TNF. We report a case of a female patient with previous diagnosis of RA for 16 years that used several disease-modifying anti-rheumatic drugs (DMARDs) that resulted in treatment failure, and then was treated with infliximab. After fifteen days of the second dose, the patient developed ventilatory-dependent chest pain, dry cough and dyspnea. She was hospitalized, and the diagnosis of pneumonia by Legionella pneumophila was confirmed by the presence of Legionella antigen in an urine test. TNF is an inflammatory cytokine that also acts inhibiting the bacterial growth of intracellular pathogens, and its inhibition seems to increase susceptibility to these infections in some patients.
Assuntos
Humanos , Feminino , Doença dos Legionários/induzido quimicamente , Antirreumáticos/efeitos adversos , Infliximab/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Antirreumáticos/uso terapêutico , Infliximab/uso terapêutico , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Opportunistic waterborne pathogens (eg, Legionella, Pseudomonas) may persist in water distribution systems despite municipal chlorination and secondary disinfection and can cause health care-acquired infections. Point-of-use (POU) filtration can limit exposure to pathogens; however, their short maximum lifetime and membrane clogging have limited their use. METHODS: A new faucet filter rated at 62 days was evaluated at a cancer center in Northwestern Pennsylvania. Five sinks were equipped with filters, and 5 sinks served as controls. Hot water was collected weekly for 17 weeks and cultured for Legionella, Pseudomonas, and total bacteria. RESULTS: Legionella was removed from all filtered samples for 12 weeks. One colony was recovered from 1 site at 13 weeks; however, subsequent tests were negative through 17 weeks of testing. Total bacteria were excluded for the first 2 weeks, followed by an average of 1.86 log reduction in total bacteria compared with controls. No Pseudomonas was recovered from filtered or control faucets. CONCLUSION: This next generation faucet filter eliminated Legionella beyond the 62 day manufacturers' recommended maximum duration of use. These new POU filters will require fewer change-outs than standard filters and could be a cost-effective method for preventing exposure to Legionella and other opportunistic waterborne pathogens in hospitals with high-risk patients.
Assuntos
Filtração/métodos , Legionella/isolamento & purificação , Sistemas Automatizados de Assistência Junto ao Leito , Pseudomonas/isolamento & purificação , Microbiologia da Água , Purificação da Água/métodos , Abastecimento de Água , Infecções Bacterianas/prevenção & controle , Carga Bacteriana , Instalações de Saúde , Pennsylvania , Fatores de TempoRESUMO
The antagonists of tumour necrosis factor (anti-TNF) have been successfully used in several chronic inflammatory diseases such as Rheumatoid Arthritis (RA), but some studies have observed the development of infections by intracellular pathogens in patients using anti-TNF. We report a case of a female patient with previous diagnosis of RA for 16 years that used several disease-modifying anti-rheumatic drugs (DMARDs) that resulted in treatment failure, and then was treated with infliximab. After fifteen days of the second dose, the patient developed ventilatory-dependent chest pain, dry cough and dyspnea. She was hospitalized, and the diagnosis of pneumonia by Legionella pneumophila was confirmed by the presence of Legionella antigen in an urine test. TNF is an inflammatory cytokine that also acts inhibiting the bacterial growth of intracellular pathogens, and its inhibition seems to increase susceptibility to these infections in some patients.
Assuntos
Antirreumáticos/efeitos adversos , Infliximab/efeitos adversos , Doença dos Legionários/induzido quimicamente , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Feminino , Humanos , Infliximab/uso terapêutico , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
Objective. To determine the interrelationship between health & hygiene conditions for prevention of legionellosis, the composition of materials used in water distribution systems, the water origin and Legionella pneumophila risk. Material and methods. Include a descriptive study and multiple regression analysis on a sample of golf course sprinkler irrigation systems (n=31) pertaining to hotels located on the Costa del Sol (Malaga, Spain). The study was carried out in 2009. Results. Presented a significant lineal relation, with all the independent variables contributing significantly (p<0.05) to the model's fit. The relationship between water type and the risk of Legionella, as well as the material composition and the latter, is lineal and positive. In contrast, the relationship between health-hygiene conditions and Legionella risk is lineal and negative. Conclusion. The characterization of Legionella pneumophila concentration, as defined by the risk in water and through use of the predictive method, can contribute to the consideration of new influence variables in the development of the agent, resulting in improved control and prevention of the disease.
Objetivo. Determinar el riesgo de Legionella pneumophila en relación a las condiciones higiénico- sanitarias para la prevención de la legionelosis, la composición de los materiales conductores de agua y el origen de la misma. Material y métodos. Incluyen un estudio descriptivo y análisis de regresión múltiple realizado sobre una muestra de sistemas de riego por aspersión de campos de golf (n=31) correspondientes a hoteles ubicados en la Costa del Sol (Málaga, España). El estudio se realizó en el año 2009. Resultados. Mostraron una relación lineal significativa, contribuyendo todas las variables independientes significativamente (p<0,05) al ajuste del modelo. La relación entre el tipo de agua y el riesgo de Legionella y de la composición del material con esta última, es lineal y positiva. En cambio, es lineal y negativa para la relación entre las condiciones higiénico- sanitarias y el riesgo de Legionella. Conclusión. La caracterización de la concentración de Legionella pneumophila definida a través del riesgo de la misma en el agua y mediante el empleo del método predictivo, contribuye a la consideración de nuevas variables de influencia en el desarrollo del agente y a un mejor control y prevención de la enfermedad.
Objetivo. Determinar o risco de Legionella pneumophila em relação às condições higiénicas e sanitárias para a prevenção da legionelose, a composição dos materiais condutores da água e a origem da mesma. Materiais e métodos. Incluem uma pesquisa descritiva e uma análise de regressão múltipla realizada em uma amostra de sistemas de irrigação por aspersão de campos de golfe (n = 31) para os hotéis situados na "Costa del Sol" (Málaga, Espanha). O estudo foi realizado em 2009. Resultados. Mostraram uma relação linear significativa, contribuindo todas as variáveis independentes significativamente (p <0,05) ao ajuste do modelo. A relação entre o tipo de água e o risgo de Legionella, assim como a composição do material com esta última, é linear e positiva. Por outro lado, é linear e negativa para a relação entre as condições higiénicas e sanitárias e o risco de Legionella. Conclusão. A caracterização da concentração de Legionella pneumophila definida através do risco da mesma na água e mediante o uso do método preditivo, contribui para a consideração de novas variáveis que influenciam no desenvolvimento do agente e a um melhor controle e prevenção da doença.
Assuntos
Doença dos Legionários , Legionella pneumophilaRESUMO
Innate immune cells, such as macrophages, are highly adapted to rapidly recognize infections by distinct pathogens, including viruses, bacteria, fungi, and protozoa. This recognition is mediated by pattern recognition receptors (PRRs), which are found in host cell surface membranes and the host cell cytoplasm. PRRs include protein families such as the toll-like receptors, nod-like receptors, RIG-I-like receptors, and sensors of cytosolic DNA. The activation of these PRRs by pathogen-associated molecular patterns leads to transcriptional responses and specific forms of cell death. These processes effectively contribute to host resistance to infection either via cell-autonomous processes that lead to the intracellular restriction of microbial replication and/or by activating pathogen-specific adaptive immune responses. Legionella pneumophila, the causative agent of Legionnaires' disease, is a Gram-negative bacterium that triggers responses by multiple PRRs. Here, we review a set of studies that have contributed to our specific understanding of the molecular mechanisms by which innate immune cells recognize and respond to L. pneumophila and the importance of these processes to the outcome of infection.
RESUMO
La presencia de cualquier microorganismo en las aguas utilizadas en las unidades dentales constituye un grave peligro tanto para el paciente como para el personal que labora en dichas unidades. La presente investigación planteó dos objetivos: 1) Implementar y comparar dos técnicas de Análisis Microbiológico del agua para el estudio de las especies de Legionella; y 2) Detectar la presencia de Legionella en el agua utilizada en las piezas de mano de las clínicas odontológicas utilizadas por los estudiantes de Odontología de la Universidad del Zulia. Se estandarizaron dos técnicas comparativas: CDC y la ISO-11731, mediante el uso de muestras preparadas con una cepa de Legionella pneumophila ATCC 33155 y se realizó un estudio bacteriológico de 40 muestras del agua de cuatro (4) clínicas odontológicas docentes ubicadas en la Facultad de Odontología de LUZ, utilizando las dos metodologías antes mencionadas. Los resultaron mostraron que ambas técnicas resultaron sensibles para el aislamiento de Legionella en muestras de agua, siendo el tratamiento ácido más efectivo que el calentamiento. A pesar del uso de estas dos técnicas no se detectó la presencia de Legionella en ninguna de las muestras de agua analizadas. La presente investigación sirvió de base para la implementación de control de calidad relacionado con el aislamiento de Legionella en las aguas utilizadas a nivel hospitalario
The presence of any microorganism in the water used in dental units constitutes a serious danger for both the patient and the personnel that work there. The present investigation had two aims: 1) To implement and compare two microbiological water analysis techniques for studying the Legionella species; and 2) To detect the presence of Legionella in the water used for hand-held equipment in dental clinics used by dentistry students at the University of Zulia. Two comparative techniques were standardized: CDC and ISO-11731, using samples prepared with the Legionella pneumophila strain ATCC 33155 and a bacteriological study of 40 water samples from four (4) dentistry teaching clinics located in the Faculty of Dentistry at LUZ, using the two aforementioned methodologies. Results showed that both techniques were sensitive to isolating Legionella in water samples, but the acid treatment was more effective than warming. Despite the use of both techniques, the presence of Legionella was not detected in any of the water samples analyzed. This study served as a basis for implementing quality control related to isolating Legionella in the waters used on a hospital level