Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 328
Filtrar
1.
Cell Host Microbe ; 26(3): 412-425.e5, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31492656

RESUMO

Surviving infection requires immune and repair mechanisms. Developing organisms face the additional challenge of integrating these mechanisms with tightly controlled developmental processes. The larval Drosophila midgut lacks dedicated intestinal stem cells. We show that, upon infection, larvae perform limited repair using adult midgut precursors (AMPs). AMPs differentiate in response to damage to generate new enterocytes, transiently depleting their pool. Developmental delay allows for AMP reconstitution, ensuring the completion of metamorphosis. Notch signaling is required for the differentiation of AMPs into the encasing, niche-like peripheral cells (PCs), but not to differentiate PCs into enterocytes. Dpp (TGF-ß) signaling is sufficient, but not necessary, to induce PC differentiation into enterocytes. Infection-induced JAK-STAT pathway is both required and sufficient for differentiation of AMPs and PCs into new enterocytes. Altogether, this work highlights the constraints imposed by development on an organism's response to infection and demonstrates the transient use of adult precursors for tissue repair.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila/crescimento & desenvolvimento , Drosophila/metabolismo , Trato Gastrointestinal/metabolismo , Larva/metabolismo , Animais , Diferenciação Celular , Modelos Animais de Doenças , Drosophila/microbiologia , Drosophila/fisiologia , Proteínas de Drosophila/genética , Enterócitos/metabolismo , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/patologia , Infecções por Bactérias Gram-Negativas/metabolismo , Infecções por Bactérias Gram-Negativas/patologia , Janus Quinases/metabolismo , Larva/imunologia , Larva/microbiologia , Metamorfose Biológica , Pectobacterium carotovorum/patogenicidade , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais/fisiologia , Células-Tronco/metabolismo , Fatores de Transcrição/metabolismo , Transcriptoma
2.
Fish Shellfish Immunol ; 94: 548-557, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31539573

RESUMO

A 56-day growth trial was conducted to investigate the effects of dietary yeast hydrolysate on the growth performance, antioxidation, immune response and resistance against Aeromonas hydrophila in largemouth bass. Four experimental diets were prepared with yeast hydrolysate levels of 0% (Y0), 1.5% (Y1.5), 3.0% (Y3.0) and 4.5% (Y4.5). Each diet was randomly assigned to triplicate 150-L tanks and each tank was stocked with 30 largemouth bass (initial body weight, IBW = 7.71 ±â€¯0.02 g). A challenge test was carried out after the feeding trial by injecting A. hydrophila intraperitoneally for 4-day observation. The results showed that the FBW and WGR in Y1.5 group were significantly higher than those in Y0 group (P < 0.05) and the feed conversion ratio (FCR) got the lowest value in Y1.5 group. And the hydrolysate supplement significantly increased the 4-day cumulative survival rate after the bacterial challenge (P < 0.05). The plasma malondialdehyde was lower in the yeast hydrolysate supplement groups in both pre- and post-challenge test (P < 0.05), while the plasma C3 increased (P < 0.05). In post-challenge test, the plasma superoxide dismutase (SOD) and catalase (CAT) activities increased in the Y1.5 and Y3.0 groups respectively (P < 0.05), and plasma lysozyme in Y1.5 group and the plasma IgM in Y3.0 group were higher than those in others respectively (P < 0.05). For the q-PCR results, in post-challenge test, the hepatic hep2 expression level in Y1.5 and Y4.5 groups were both significantly higher than those in others (P < 0.05), as well as il-8 in Y3.0 group. The spleen hif-1alpha and tgf-beta1 expression levels in Y4.5 group were all significantly lower than those in others (P < 0.05), while the gilt was significantly higher (P < 0.05) in the post-challenge test. And the expression levels of spleen tnf-alpah1 in Y1.5 and Y3.0 groups and il-8 in Y3.0 group were all significantly higher than those in other groups (P < 0.05) in the post-challenge test. The head kidney gilt expression level was significantly higher in the yeast hydrolysate supplement groups compared with the Y0 group (P < 0.05), and the head kidney il-8 expression level in Y1.5 group was significant higher than those in other groups in post-challenge test (P < 0.05). The present results indicated dietary yeast hydrolysate improved the antioxidant ability and enhanced the immune response of largemouth bass without negative effect on growth. And 1.5% or 3.0% of dietary yeast hydrolysate was recommended for largemouth bass based on the present results.


Assuntos
Bass , Resistência à Doença/efeitos dos fármacos , Doenças dos Peixes/imunologia , Expressão Gênica/imunologia , Infecções por Bactérias Gram-Negativas/veterinária , Fermento Seco/metabolismo , Aeromonas hydrophila/fisiologia , Ração Animal/análise , Animais , Bass/crescimento & desenvolvimento , Dieta/veterinária , Suplementos Nutricionais/análise , Doenças dos Peixes/genética , Doenças dos Peixes/metabolismo , Infecções por Bactérias Gram-Negativas/genética , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/metabolismo , Fermento Seco/administração & dosagem
3.
Artigo em Inglês | MEDLINE | ID: mdl-31454703

RESUMO

This research aimed to assess the influence of dietary addition of rutin on inflammation, apoptosis and antioxidative responses in muscle of silver catfish (Rhamdia quelen) challenged with Aeromonas hydrophila (A. hydrophila). Fish were split into four groups as follows: control, 0.15% rutin, A. hydrophila, 0.15% rutin + A. hydrophila. After 2 weeks of feeding with standard or rutin diets, fish were challenged or not with A. hydrophila for 1 week. Rutin-added diet abrogates A. hydrophila induced-hemorrhage and inflammatory infiltration. It decreases A. hydrophila induced-apoptosis through decreasing the ratio of Bax to Bcl-2 and increasing phospho-Akt to Akt ratio. It diminishes the A. hydrophila induced-rise in nitric oxide and superoxide anion levels and reestablishes superoxide dismutase activity as well. Although such diet is unable to recover the levels of reduced glutathione (GSH), cysteine and glutamate cysteine ligase, which are depleted as a result of A. hydrophila infection, it diminishes the oxidized glutathione (GSSG) content, thus decreasing GSSG to GSH ratio. It increases the levels of cysteine residues of proteins and diminishes those of thiol-protein mixed disulfides, which were changed after A. hydrophila challenge. Finally, it reduces A. hydrophila induced-lipid peroxidation, markedly elevates ascorbic acid and thus reestablishes total antioxidant capacity, whose levels were decreased after A. hydrophila challenge. In conclusion, the dietary addition of rutin at 0.15% impairs A. hydrophila-induced inflammatory response, inhibits A. hydrophila-induced apoptosis and promotes cell survival. It also reduces the A. hydrophila-induced oxidative stress and stimulates the antioxidative responses in muscle of A. hydrophila-infected silver catfish.


Assuntos
Peixes-Gato/imunologia , Doenças dos Peixes/metabolismo , Infecções por Bactérias Gram-Negativas , Músculos/metabolismo , Rutina/farmacologia , Aeromonas hydrophila , Ração Animal , Animais , Antioxidantes/farmacologia , Apoptose , Suplementos Nutricionais , Infecções por Bactérias Gram-Negativas/metabolismo , Infecções por Bactérias Gram-Negativas/veterinária , Estresse Oxidativo , Substâncias Protetoras/farmacologia
4.
Artigo em Inglês | MEDLINE | ID: mdl-31192158

RESUMO

The superbacteria Aeromonas veronii displays not only a strong pathogenicity but also the resistance to nine kinds of antibiotics, resulting in the economic losses and health hazards. Small Protein B (SmpB) plays an important role in protein quality control, virulence, and stress reactions. Transcriptomic data revealed that expressions of the type IV pilus assembly and type VI secretion system (T6SS) proteins were downregulated in SmpB deficiency, indicating that the virulence of A. veronii might be attenuated. Although SmpB deletion decreased colonization in the mouse spleen and liver, LD50 of the smpB mutant was not altered as expected, compared with the wild type. Further, the transcriptomic and quantitative RT-PCR analyses showed that the combination of the downregulated AvrA and the upregulated iron-sulfur protein activator IscR, mediated the oxidative tolerance in smpB deletion. Next a reporter plasmid was constructed in which the promoter of iscR was applied to control the expression of the enhanced green fluorescent protein (eGFP) gene. When the reporter plasmid was co-expressed with the AvrA expression into E. coli, the relative fluorescence intensity was decreased significantly, suggesting that AvrA bound to iscR mRNA by base pairing, which in turn relieved the inhibition of iscR and intensified the downstream iron-sulfur proteins. Collectively, the smpB mutant exhibited an attenuated virulence in mice and enhanced tolerances to oxidative stress. This study demonstrates the complexity of gene regulation networks mediated by sRNA in systems biology, and also reflects the strong adaptability of superbacteria A. veronii in the process of evolution.


Assuntos
Aeromonas veronii/metabolismo , Proteínas de Bactérias/metabolismo , RNA Bacteriano/metabolismo , Proteínas de Ligação a RNA/metabolismo , Estresse Fisiológico/fisiologia , Fatores de Transcrição/metabolismo , Aeromonas veronii/genética , Animais , Proteínas de Bactérias/genética , Sítios de Ligação , Modelos Animais de Doenças , Regulação para Baixo , Escherichia coli/genética , Deleção de Genes , Regulação Bacteriana da Expressão Gênica , Infecções por Bactérias Gram-Negativas/metabolismo , Proteínas com Ferro-Enxofre/metabolismo , Dose Letal Mediana , Fígado/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Estresse Oxidativo , Regiões Promotoras Genéticas , Proteínas de Ligação a RNA/genética , Baço/microbiologia , Sistemas de Secreção Tipo VI/metabolismo , Virulência
6.
Life Sci Alliance ; 2(2)2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30902833

RESUMO

Intracellular bacteria that live in host cell-derived vacuoles are significant causes of human disease. Parasitism of low-density lipoprotein (LDL) cholesterol is essential for many vacuole-adapted bacteria. Acid sphingomyelinase (ASM) influences LDL cholesterol egress from the lysosome. Using functional inhibitors of ASM (FIASMAs), we show that ASM activity is key for infection cycles of vacuole-adapted bacteria that target cholesterol trafficking-Anaplasma phagocytophilum, Coxiella burnetii, Chlamydia trachomatis, and Chlamydia pneumoniae. Vacuole maturation, replication, and infectious progeny generation by A. phagocytophilum, which exclusively hijacks LDL cholesterol, are halted and C. burnetii, for which lysosomal cholesterol accumulation is bactericidal, is killed by FIASMAs. Infection cycles of Chlamydiae, which hijack LDL cholesterol and other lipid sources, are suppressed but less so than A. phagocytophilum or C. burnetii A. phagocytophilum fails to productively infect ASM-/- or FIASMA-treated mice. These findings establish the importance of ASM for infection by intracellular bacteria and identify FIASMAs as potential host-directed therapies for diseases caused by pathogens that manipulate LDL cholesterol.


Assuntos
Desipramina/farmacologia , Inibidores Enzimáticos/farmacologia , Bactérias Gram-Negativas/patogenicidade , Infecções por Bactérias Gram-Negativas/metabolismo , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Esfingomielina Fosfodiesterase/antagonistas & inibidores , Esfingomielina Fosfodiesterase/metabolismo , Animais , LDL-Colesterol/metabolismo , Modelos Animais de Doenças , Células Endoteliais/microbiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Células HeLa , Voluntários Saudáveis , Humanos , Macaca mulatta , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neutrófilos/microbiologia , Transdução de Sinais/efeitos dos fármacos , Esfingomielina Fosfodiesterase/genética , Células THP-1 , Vacúolos/metabolismo , Vacúolos/microbiologia
7.
Artigo em Inglês | MEDLINE | ID: mdl-30710691

RESUMO

Francisellosis is a disease produced by Francisella spp. which affects farmed fish. Eleginops maclovinus specimens can be caught close to salmon farming centers, feeding on un-consumed pellet, making the transmission of pathogens such as Francisella noatunensis possible. The aim of this study was to evaluate the effect of F. noatunensis on liver intermediary metabolism in E. maclovinus. 144 fish were injected intraperitoneally with F. noatunensis at a low dose LD (1 × 101 cells/µL), medium dose MD (1 × 105 cells/µL), high dose HD (1 × 1010 cells/µL), or with culture medium C (control), and sampled at 1, 3, 7, 14, 21 and 28 days post injection (dpi). No mortality was recorded during the experimental period, but there was a marked metabolic response in fish injected with high doses. Metabolites in plasma were lowest in the high bacterial dose. Cortisol levels were highest at day 7 in the high dose and then decreased from day 14 until the end of the study. Liver enzymes showed a similar pattern to plasma metabolites, with decreased enzymatic activity, mostly with the high bacteria dose. PK was the exception, with increased enzymatic activity in a dose-dependent manner over time. Liver metabolites were highly variable, except in the high bacterial dose where variability and total levels decreased significantly. Our results show that fish infection with F. noatunensis induces a clear stress response, especially with at the highest dose, shifting intermediary metabolism towards mobilization of energy and suggesting that E. maclovinus detects experimental infection of F. noatunensis as a stressor, which it is dependent on the bacterial dose.


Assuntos
Doenças dos Peixes/metabolismo , Francisella/patogenicidade , Infecções por Bactérias Gram-Negativas/metabolismo , Fígado/metabolismo , Fígado/patologia , Perciformes/metabolismo , Estresse Fisiológico , Animais , Doenças dos Peixes/microbiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Injeções Intraperitoneais , Fígado/microbiologia , Perciformes/microbiologia
8.
Arch. argent. pediatr ; 117(1): 6-11, feb. 2019. tab
Artigo em Inglês, Espanhol | LILACS, BINACIS | ID: biblio-983770

RESUMO

Introducción. Las infecciones por bacilos Gram-negativos multirresistentes (BGN-MR) constituyen un problema creciente en las unidades de cuidado intensivo neonatal. El objetivo del estudio fue conocer las características epidemiológicas, clínicas, microbiológicas, evolutivas y los factores de riesgo de infección por BGN-MR resistentes a carbapenemes en el Servicio de Neonatología de un hospital de alta complejidad. Población y método. Se realizó un estudio de cohorte retrospectivo en dicho Servicio, donde se incluyeron los pacientes con infección documentada por BGN-MR del 24/4/2013 al 29/4/2015. Resultados. Se incluyeron 21 pacientes. La mediana de edad gestacional y peso de nacimiento fue 35 semanas y 2070 gramos, respectivamente. Dieciocho pacientes (86 %) tuvieron hemocultivos positivos y el aislamiento microbiológico más frecuente fue Acinetobacter baumannii (17 pacientes, 81 %), seguido por Klebsiella pneumoniae productora de carbapenemasa (3 pacientes, 14 %) y Enterobacter cloacae (1 paciente, 5 %). La mediana de edad al momento del diagnóstico fue de 28 días y todos tenían factores de riesgo para la infección, como cirugía, asistencia respiratoria mecánica, nutrición parenteral, catéter central y antibióticos. El tratamiento antibiótico definitivo fue colistina en todos los casos, combinado en el 84 %. Cinco pacientes (24 %) fallecieron por la infección. La prematurez y el peso < 2000 g fueron factores de riesgo estadísticamente significativos asociados a la mortalidad (p = 0,03 y 0,01, respectivamente). Conclusión. Las infecciones por BGN-MR se presentaron en pacientes con factores predisponentes. Acinetobacter baumannii fue el primer agente etiológico. La mortalidad fue elevada y relacionada con prematurez y bajo peso al nacer.


Introduction. Multidrug resistant Gramnegative (MDRGN) infections are an increasing problem in neonatal intensive care units. The objective of this study was to establish the epidemiological, clinical, microbiological, and evolutionary characteristics of carbapenem-resistant MDRGN infections and the risk factors for them at the Division of Neonatology of a tertiary care hospital. Population and method. A retrospective cohort study was done in this Division in patients with a documented MDRGN infection between 4/24/2013 and 4/29/2015. Results. Twenty-one patients were included. Their median gestational age and birth weight were 35 weeks and 2070 g, respectively. Eighteen patients (86 %) had a positive blood culture; the most commonly isolated microorganism was Acinetobacter baumannii (17 patients, 81 %), followed by carbapenemase-producing Klebsiella pneumoniae (3 patients, 14 %) and Enterobacter cloacae (1 patient, 5 %). The median age at diagnosis was 28 days and all patients had risk factors for infection, including surgery, assisted mechanical ventilation, parenteral nutrition, central venous line, and antibiotics. The definite antibiotic therapy included colistin in all cases; in combination, in 84 %. Five patients (24 %) died due to the infection. Prematurity and a birth weight < 2000 g were statistically significant risk factors associated with mortality (p = 0.03 and 0.01, respectively). Conclusion. MDRGN infections were observed in patients with predisposing factors. Acinetobacter baumannii was the main etiologic agent. Mortality was high and related to prematurity and a low birth weight.


Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Infecções por Bactérias Gram-Negativas/metabolismo , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/epidemiologia , Epidemiologia Descritiva , Estudos Retrospectivos , Farmacorresistência Bacteriana Múltipla , Bactérias Gram-Negativas/metabolismo
9.
BMC Res Notes ; 12(1): 38, 2019 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-30658694

RESUMO

OBJECTIVES: Gram-negative bacilli are the common causative agents for community-acquired, nosocomial and opportunistic infections. The recent upsurge of biofilm, as well as beta-lactamases producing strains, have synergistically led to the extensive dissemination of multi-drug resistant gram-negative bacilli. This study was carried out with an intention to detect the biofilm formation by gram-negative bacilli and determine their antibiogram along with the detection of extended-spectrum beta-lactamases (ESBLs) and metallo-beta-lactamases (MBLs) production. RESULTS: Among 314 isolates, Escherichia coli (38%) were the predominant isolates followed by Acinetobacter spp. (20%), Klebsiella spp. (16%), and Pseudomonas spp. (12%). Overall, 197 (62.73%) of isolates were biofilm positive. 84 (26.75%) and 51 (16.24%) were confirmed as ESBL and MBL producers respectively. The association between MBL production and biofilm formation was statistically significant (χ2 = 10.20, P value= 0.002) whereas it was insignificant between ESBL and biofilm production (χ2 = 0.006, P-value= 0.937). Most of the biofilm and MBL producing strains were multi-drug resistant.


Assuntos
Biofilmes/efeitos dos fármacos , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Acinetobacter/efeitos dos fármacos , Acinetobacter/metabolismo , Acinetobacter/fisiologia , Antibacterianos , Proteínas de Bactérias/metabolismo , Biofilmes/crescimento & desenvolvimento , Escherichia coli/efeitos dos fármacos , Escherichia coli/metabolismo , Escherichia coli/fisiologia , Bactérias Gram-Negativas/classificação , Bactérias Gram-Negativas/fisiologia , Infecções por Bactérias Gram-Negativas/metabolismo , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Nepal , beta-Lactamases/metabolismo
10.
Artigo em Inglês | MEDLINE | ID: mdl-30665028

RESUMO

Photobacterium damselae subsp. piscicida (P. damselae subsp. piscicida) is the agent of Photobacteriosis, a serious fish disease that produces an acute infection and high mortality in farmed cobia. It has been proved that regulation of pro- and anti-inflammatory cytokines play a central role in initiation of proper inflammatory responses against bacterial infection. Here we have analyzed the expression of pro-inflammatory cytokines (IL-1ß, TNF-α, IL-6, IL-8 and IFN-ɤ) and anti-inflammatory cytokines (IL-10 and IL-11) in spleen and head kidney during acute P. damselae subsp. piscicida infection of cobia. Our data revealed that cytokines tested showed distinct patterns of expression. While TNF-α and IL-8 showed a decay pattern of expression, IL-1ß response was quite late. Moreover, P. damselae subsp. piscicida infection induced the simultaneous expressions of pro-inflammatory (IL-6, IFN-ɤ) and anti-inflammatory (IL-10, IL-11) cytokines. Together these results indicate the innate immunity of cobia is actively suppressed by P. damselae subsp. piscicida.


Assuntos
Citocinas/metabolismo , Doenças dos Peixes/metabolismo , Proteínas de Peixes/metabolismo , Infecções por Bactérias Gram-Negativas/metabolismo , Mediadores da Inflamação/metabolismo , Perciformes/metabolismo , Photobacterium/fisiologia , Animais , Doenças dos Peixes/imunologia , Doenças dos Peixes/microbiologia , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/microbiologia , Interferon gama/metabolismo , Interleucina-10/metabolismo , Interleucina-11/metabolismo , Interleucina-6/metabolismo , Perciformes/microbiologia
11.
Artigo em Inglês | MEDLINE | ID: mdl-30695731

RESUMO

Milkfish (Chanos chanos Forsskal) is an important aquaculture product and is the sole extant species of the family Chanidae (order Gonorynchiformes). While there are already several reports regarding milkfish aquaculture, studies on milkfish immunity and gene expression are very limited. In this study, we showed that Aeromonas hydrophila induces inflammation in milkfish liver. We identified a milkfish C-type lectin-like domain containing proteins (CTLDcps) gene, designated as CcClec, which was upregulated in respond to A. hydrophila. Full-length sequencing was performed using Rapid Amplification of cDNA Ends (RACE PCR) to produce a complete Coding DNA Sequence (CDS) of the gene. The CcClec gene encoded a predicted protein of 340 amino acids containing two CTLDs that may potentially bind carbohydrates, especially sucrose and cellobiose. The CcClec mRNA transcript was expressed highest in the liver, followed by head kidney, brain, heart, gills, spleen, and midgut. CcClec transcripts were upregulated in damaged liver upon exposure to A. hydrophila. Overall, these findings demonstrated that CcClec is implicated in milkfish innate immunity, and is most highly expressed in the liver, suggesting a role of the liver in the milkfish immune system.


Assuntos
Doenças dos Peixes/imunologia , Proteínas de Peixes/metabolismo , Peixes/imunologia , Infecções por Bactérias Gram-Negativas/complicações , Inflamação/imunologia , Lectinas Tipo C/metabolismo , Fígado/imunologia , Aeromonas hydrophila/fisiologia , Animais , Doenças dos Peixes/metabolismo , Doenças dos Peixes/microbiologia , Proteínas de Peixes/genética , Peixes/metabolismo , Peixes/microbiologia , Regulação da Expressão Gênica , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/metabolismo , Inflamação/metabolismo , Inflamação/microbiologia , Lectinas Tipo C/genética , Fígado/metabolismo , Fígado/microbiologia , Filogenia
12.
Gene ; 686: 68-75, 2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30342169

RESUMO

Interleukin-17 (IL17) family cytokines are well known for having pro-inflammatory actions as important mediators of mucosal immune responses and are tightly regulated by various kinds of signals. However, most studies of IL17 genes have focused on mammals, and much less is known about IL17 genes in fish species. To better understand the scope and actions of the IL17 gene family in common carp, we characterized seven IL17 gene homologs from genomic and transcriptomic databases that could be classified into three subclasses according to different comparative genomic analyses. Phylogenetic analysis revealed that most IL17s are highly conserved, though recent gene duplication and gene loss events do exist. Through observation, we found that IL17D has undergone gene duplication in common carp and that all the IL17E genes were lost in vertebrates except mammals. The expression patterns of IL17 genes in common carp were examined during early developmental stages and in various healthy tissues, and the results indicated that most IL17 genes are ubiquitously expressed during early development and show particular tissue-specific expression in various healthy tissues, with relatively high levels in the spleen, liver, and kidney. To gain insights into the mucosal actions of inflammatory processes, the expression profiles of IL17 genes in gills from common carp were investigated after experimental challenge with Aeromonas hydrophila. After A. hydrophila infection, most IL17 genes were upregulated at 4 h postinfection in the gill and then gradually declined, while IL17A/F2 and IL17N were generally upregulated at 12 h postinfection, and IL17D2 maintained an increasing tendency. In contrast, IL17D showed the third phenomenon, rising expression, suggesting that immunogenes have different response strategies to bacterial invasion. Overall, the expression of IL17 in unstimulated tissues and toxicity attack test results demonstrated that these genes play critical roles under normal conditions and during bacterial infection. Moreover, this common carp IL17 gene family research provides a genomic resource for future studies on IL17 gene evolution, fish disease management and immune regulation.


Assuntos
Aeromonas hydrophila , Carpas , Doenças dos Peixes , Proteínas de Peixes , Infecções por Bactérias Gram-Negativas , Interleucina-17 , Animais , Carpas/genética , Carpas/metabolismo , Carpas/microbiologia , Doenças dos Peixes/genética , Doenças dos Peixes/metabolismo , Doenças dos Peixes/microbiologia , Doenças dos Peixes/patologia , Proteínas de Peixes/biossíntese , Proteínas de Peixes/genética , Estudo de Associação Genômica Ampla , Infecções por Bactérias Gram-Negativas/genética , Infecções por Bactérias Gram-Negativas/metabolismo , Infecções por Bactérias Gram-Negativas/patologia , Infecções por Bactérias Gram-Negativas/veterinária , Interleucina-17/biossíntese , Interleucina-17/genética
13.
Fish Shellfish Immunol ; 86: 107-115, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30447430

RESUMO

Complement system is an immemorial and pivotal element in innate immunity, protecting individuals from invading pathogens. Due to the emergence of whole genomes and functional researches, systematic identifications of complement system are feasible in many non-model species. In the present study, BLAST analysis was employed to systematically identify and characterize complement system in grass carp (Ctenopharyngodon idella). The results showed that C. idella complement system consists of 64 members, including the complement system pattern recognition, proteases, complement components, receptors and regulators. In which, most genes were well conserved with those in higher vertebrates over the course of evolution. Phylogenetic and syntenic analyses revealed their homologous relationships with other species. mRNA expression analyses of complement system related genes indicated that many members are sustainably expressed in multiple tissues before and after grass carp reovirus (GCRV) or Aeromonas hydrophila infection, which provide in vivo evidence for the response patterns of complement system after viral or bacterial infection. Meanwhile, this study also explored the evolution of complement system from ancestral protists to mammals and then investigated the changes in gene diversification during the evolution. These results will serve the comparative studies on the complement system in evolution and further functional investigations in C. idella.


Assuntos
Carpas , Proteínas do Sistema Complemento/metabolismo , Doenças dos Peixes/metabolismo , Proteínas de Peixes/metabolismo , Infecções por Bactérias Gram-Negativas/veterinária , Infecções por Reoviridae/veterinária , Aeromonas hydrophila , Animais , Proteínas do Sistema Complemento/genética , Proteínas de Peixes/genética , Regulação da Expressão Gênica , Infecções por Bactérias Gram-Negativas/metabolismo , Infecções por Bactérias Gram-Negativas/microbiologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reoviridae , Infecções por Reoviridae/metabolismo , Infecções por Reoviridae/virologia , Transcriptoma
14.
Ther Drug Monit ; 41(1): 44-52, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30299427

RESUMO

BACKGROUND: Amikacin is widely used to treat severe Gram-negative bacterial infections. Its peak concentration in plasma is associated with treatment efficacy. Amikacin pharmacokinetics (PK) is influenced by disease conditions, in addition to other patient characteristics. In this retrospective study, we evaluated the impact of clinical characteristics and disease condition on amikacin PK in children with burn injuries and those with cancer. METHODS: Amikacin PK data from 66 children with burn injuries and 112 children with cancer were analyzed. A population PK model was developed using the nonlinear mixed-effects modeling approach. Models were developed using NONMEM 7.3 (ICON Development Solutions, LLC, Ellicott City, MD). Data processing and visualization was performed using R packages. RESULTS: The amikacin PK data were best described by a 2-compartment model. The parameters were estimated with mean values (95% confidence intervals) as follows: central volume of distribution (V1), 5.70 L (4.64-6.76 L); central clearance, 2.12 L/h (1.79-2.46 L/h); peripheral volume of distribution (V2), 4.79 L (2.36-7.22 L); and distribution clearance (Q), 0.71 L/h (0.25-1.16 L/h). The final model identified the disease condition as a significant covariate and indicated 55% (28%-82%) higher central clearance and 17% (1%-34%) higher V1 in burn patients compared with cancer patients. Volume of distribution was significantly influenced by age and body weight. Clearance was significantly influenced by age, body weight, and creatinine clearance. Using the final PK model, we developed a workflow for selecting optimal dosing strategies for 3 representative pediatric patient profiles. CONCLUSIONS: Disease condition was significant in influencing amikacin PK in children. To reach the same target concentrations (64 mg/L peak concentration) with a daily-dose plan, burn patients need higher doses than cancer patients. Future investigations are needed to explore the impact of other diseases on amikacin disposition in children, and to prospectively validate the proposed dosing strategy.


Assuntos
Amicacina/farmacocinética , Antibacterianos/farmacocinética , Queimaduras/metabolismo , Neoplasias/metabolismo , Adolescente , Amicacina/uso terapêutico , Queimaduras/sangue , Criança , Pré-Escolar , Feminino , Infecções por Bactérias Gram-Negativas/sangue , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/metabolismo , Humanos , Lactente , Masculino , Neoplasias/sangue , Estudos Retrospectivos
15.
Ther Drug Monit ; 41(1): 102-106, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30299430

RESUMO

BACKGROUND: Colistin is increasingly used as the last therapeutic option for the treatment of multidrug-resistant, Gram-negative bacterial infections. To ensure safe and efficacious use of colistin, therapeutic drug monitoring (TDM) is needed due to its narrow therapeutic window. This study aimed to evaluate the pharmacokinetic (PK) characteristics of colistin and to guide TDM in colistin-treated patients in Korea. METHODS: In a prospective study, we analyzed PK characteristics in 15 patients who intravenously received colistin methanesulfonate twice per day. Colistin methanesulfonate doses were adjusted based on renal function of the subjects. The appropriate blood sampling points for TDM were evaluated by analyzing the correlations between the PK parameters and the plasma concentrations at each time point. RESULTS: The mean values for the minimum, maximum, and average concentrations (Cmin, Cmax, and Caverage) of colistin at steady state were 2.29, 5.5, and 3.38 mg/L, respectively. The dose-normalized Cmin, Cmax, Caverage, and area under the plasma concentration-time curve from 0 to the last measurable concentration (AUClast) showed negative correlations with the creatinine clearance. The combination of the 0- and 2-hour post-dose plasma concentrations was evaluated as the appropriate sampling point for TDM. Two patients reported nephrotoxic adverse events during colistin administration. CONCLUSIONS: Our study clarifies the PK characteristics of successful colistin treatment using TDM. Further evaluations in a larger patient population are needed to confirm the clinical usefulness of colistin TDM.


Assuntos
Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Colistina/farmacocinética , Colistina/uso terapêutico , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Infusões Intravenosas/métodos , Masculino , Testes de Sensibilidade Microbiana/métodos , Pessoa de Meia-Idade , Estudos Prospectivos , República da Coreia
16.
Fish Shellfish Immunol ; 84: 38-47, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30261297

RESUMO

The present investigation aims to study role of dietary selenium (Se) on growth performance, oxidative stress markers (catalase, superoxide dismutase and glutathione-s-transferase), stress biomarkers [blood glucose, cortisol and heat shock protein (HSP 70) and immunological status, Nitro blue tetrazolium (NBT), total protein, albumin, globulin, A/G ratio, total immunoglobulin and vitamin C] and survival of fish after Aeromonas veronii biovar sobria challenged. Pangasianodon hypophthalmus was treated with lead (Pb, 4 ppm), and high temperature (34 °C) for 60 days. The growth performance was reduced with declined in feed intake, growth rate and feed efficiency in case of group exposed with Pb alone and concurrent exposure to Pb high temperature (34 °C). The Se has immunomodulatory properties however, supplementation of the dietary Se @ 1 and 2 mg/kg diet has been realistically improved growth performance up to 240%, elevated antioxidative status in different tissues, and immunological status were also improved significantly in the P. hypophthalmus. The bacterial challenged with A. veronii biovar sobria in the P. hypophthalmus resulting in less cumulative mortality (%) and high relative (%) survival has been observed with supplementation of dietary Se @ 1 and 2 mg/kg diet. The bioaccumulation of Pb in muscle tissue has been also drastically reduced with supplementation of dietary Se in feed. Hence, overall results indicated that, dietary Se @ 1 and 2 mg/kg have ability to enhanced overall performance and alleviated multiple stresses in P hypophthalmus.


Assuntos
Aeromonas veronii , Peixes-Gato/fisiologia , Doenças dos Peixes/metabolismo , Infecções por Bactérias Gram-Negativas/metabolismo , Selênio/administração & dosagem , Acetilcolinesterase/metabolismo , Animais , Glicemia/análise , Peixes-Gato/microbiologia , Dieta , Infecções por Bactérias Gram-Negativas/veterinária , Proteínas de Choque Térmico HSP70/metabolismo , Hidrocortisona/sangue , Chumbo/administração & dosagem , Chumbo/farmacocinética , Músculos/metabolismo , Estresse Oxidativo , Estresse Fisiológico/fisiologia
17.
J Biosci Bioeng ; 127(2): 169-175, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30082220

RESUMO

The bacterial wilt pathogen Ralstonia pseudosolanacearum Ps29 exhibited chemotactic responses to citrate. This pathogen expresses 22 putative chemoreceptors. In screening a complete collection of mcp single-gene deletion mutants of Ps29, none showed a significant decrease in response to citrate compared with the wild-type strain. Analysis of a collection of stepwise- and multiple-deletion mutants of Ps29 revealed that the RS_RS07350 homolog (designated McpC) and McpP (chemoreceptor mediating both positive chemotaxis to phosphate and negative chemotaxis to maleate) are chemoreceptors for citrate. Double deletion of mcpC and mcpP markedly reduced the response to citrate, indicating that McpC and McpP are major chemoreceptors for citrate. Wild-type Ps29 was attracted to both free citrate and citrate complexed with divalent metal cations such as magnesium and calcium. The mcpC mcpP double-deletion mutant also showed significant reduction in chemotaxis to Mg2+- and Ca2+-citrate complexes. Introduction of a plasmid harboring the mcpC gene (but not the mcpP gene) restored the ability to respond to these citrate-metal complexes, demonstrating that McpC can sense complexes of citrate and metal ions such as Mg2+ and Ca2+ as well as free citrate. Thus, R. pseudosolanacearum Ps29 expresses two chemoreceptors for citrate. In plant infection assays using tomato seedlings, the mcpC and mcpP single- and double-deletion mutants of the highly virulent R. pseudosolanacearum MAFF106611 strain were as infectious as the wild-type strain, suggesting that citrate chemotaxis does not play an important role in infection of tomato plants in this assay system.


Assuntos
Ácido Cítrico/metabolismo , Complexos de Coordenação/metabolismo , Proteínas Quimiotáticas Aceptoras de Metil/genética , Ralstonia/genética , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteínas de Transporte/química , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Quimiotaxia/genética , Citratos/química , Citratos/metabolismo , Citratos/farmacologia , Ácido Cítrico/química , Ácido Cítrico/farmacologia , Clonagem Molecular , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Deleção de Genes , Infecções por Bactérias Gram-Negativas/metabolismo , Infecções por Bactérias Gram-Negativas/microbiologia , Lycopersicon esculentum/microbiologia , Metais/química , Metais/metabolismo , Proteínas Quimiotáticas Aceptoras de Metil/química , Proteínas Quimiotáticas Aceptoras de Metil/isolamento & purificação , Proteínas Quimiotáticas Aceptoras de Metil/metabolismo , Doenças das Plantas/microbiologia , Ligação Proteica/efeitos dos fármacos , Ralstonia/metabolismo , Ralstonia/patogenicidade
18.
Microbiologyopen ; 8(4): e00664, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-29897673

RESUMO

Stress is an important contributing factor in the outbreak of infectious fish diseases. To comprehensively understand the impact of catecholamine stress hormone norepinephrine (NE) on the pathogenicity of Aeromonas hydrophila, we assessed variations in bacterial growth, virulence-related genes expression and virulence factors activity after NE addition in serum-SAPI medium. Further, we assessed the effects of NE on A. hydrophila virulence in vivo by challenging fish with pathogenic strain AH196 and following with or without NE injection. The NE-associated stimulation of A. hydrophila strain growth was not linear-dose-dependent, and only 100 µM, or higher concentrations, could stimulate growth. Real-time PCR analyses revealed that NE notably changed 13 out of the 16 virulence-associated genes (e.g. ompW, ahp, aha, ela, ahyR, ompA, and fur) expression, which were all significantly upregulated in A. hydrophila AH196 (p < 0.01). NE could enhance the protease activity, but not affect the lipase activity, hemolysis, and motility. Further, the mortality of crucian carp challenged with A. hydrophila AH196 was significantly higher in the group treated with NE (p < 0.01). Collectively, our results showed that NE enhanced the growth and virulence of pathogenic bacterium A. hydrophila.


Assuntos
Aeromonas hydrophila/crescimento & desenvolvimento , Aeromonas hydrophila/patogenicidade , Doenças dos Peixes/metabolismo , Infecções por Bactérias Gram-Negativas/veterinária , Hormônios/metabolismo , Norepinefrina/metabolismo , Aeromonas hydrophila/efeitos dos fármacos , Aeromonas hydrophila/genética , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Carpas , Doenças dos Peixes/microbiologia , Infecções por Bactérias Gram-Negativas/metabolismo , Infecções por Bactérias Gram-Negativas/microbiologia , Interações Hospedeiro-Patógeno , Norepinefrina/farmacologia , Estresse Fisiológico , Virulência/efeitos dos fármacos
19.
Fish Shellfish Immunol ; 82: 173-182, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30081180

RESUMO

The innate immune response is able to ward off pathogens and remember previous infections using different mechanisms; this kind of immune reaction has been called "trained immunity". Changes in cellular metabolism (aerobic glycolysis) have been observed during training with some immunostimulants like ß-glucans or during viral and bacterial infections. We hypothesize that ß-glucans can induce metabolic changes used by the host to fight pathogens. Accordingly, we evaluated changes in metabolic parameters in turbot that could affect their survival after a previous intraperitoneal treatment with ß-glucans and subsequent administration of Viral Hemorrhagic Septicemia Virus (VHSV) or bacteria (Aeromonas salmonicida subsp. salmonicida). The results obtained support that ß-glucans, VHSV and A. salmonicida induce changes in lactate, glucose and ATP levels in plasma, head kidney and liver and in the mRNA expression of enzymes related to glucose and fatty acid metabolism in head kidney. Additionally, the metabolic changes induced by ß-glucans are beneficial for VHSV replication, but they are harmful to A. salmonicida, resulting in reduced mortality. ß-glucans appear to have great therapeutic potential and can induce trained immunity against bacterial disease but not against viral disease, which seems to take advantage of ß-glucan metabolic alterations.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Doenças dos Peixes/imunologia , Linguados , Infecções por Bactérias Gram-Negativas/veterinária , Infecções por Rhabdoviridae/veterinária , beta-Glucanas/administração & dosagem , Adjuvantes Imunológicos/farmacologia , Aeromonas salmonicida/fisiologia , Animais , Doenças dos Peixes/tratamento farmacológico , Doenças dos Peixes/metabolismo , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/metabolismo , Longevidade/efeitos dos fármacos , Novirhabdovirus/fisiologia , Distribuição Aleatória , Infecções por Rhabdoviridae/tratamento farmacológico , Infecções por Rhabdoviridae/imunologia , Infecções por Rhabdoviridae/metabolismo , beta-Glucanas/farmacologia
20.
Artigo em Inglês | MEDLINE | ID: mdl-29967021

RESUMO

To guide the timely selection of antibiotic combinations against carbapenem-resistant Gram-negative bacteria (CR-GNB), an in vitro test with a short turnaround time is essential. We developed an in vitro ATP bioluminescence assay to determine effective antibiotic combinations against CR-GNB within 6 h. We tested 42 clinical CR-GNB strains (14 Acinetobacter baumannii, 14 Pseudomonas aeruginosa, and 14 Klebsiella pneumoniae strains) against 74 single antibiotics and two-antibiotic combinations. Bacteria (approximately 5 log10 CFU/ml) were incubated with an antibiotic(s) at 35°C; ATP bioluminescence was measured at 6 h and 24 h; and the measurements were compared to viable counts at 24 h. Receiver operating characteristic (ROC) curves were used to determine the optimal luminescence thresholds (TRLU) for distinguishing between inhibitory and noninhibitory combinations. The areas under the 6-h and 24-h ROC curves were compared using the DeLong method. Prospective validation of the established thresholds was conducted using 18 additional CR-GNB. The predictive accuracy of TRLU for the 6-h ATP bioluminescence assay was 77.5% when all species were analyzed collectively. Predictive accuracies ranged from 73.7% to 82.7% when each species was analyzed individually. Upon comparison of the areas under the 6-h and 24-h ROC curves, the 6-h assay performed significantly better than the 24-h assay (P < 0.01). Predictive accuracy remained high upon prospective validation of the 6-h ATP assay (predictive accuracy, 79.8%; 95% confidence interval [CI], 77.6 to 81.9%), confirming the external validity of the assay. Our findings indicate that our 6-h ATP bioluminescence assay can provide guidance for prospective selection of antibiotic combinations against CR-GNB in a timely manner and may be useful in the management of CR-GNB infections.


Assuntos
Trifosfato de Adenosina/metabolismo , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Bactérias Gram-Negativas/metabolismo , Infecções por Bactérias Gram-Negativas/metabolismo , Humanos , Medições Luminescentes/métodos , Estudos Prospectivos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA