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[PMID]:29458554
[Au] Autor:Osaka S; Okuzumi K; Koide S; Tamai K; Sato T; Tanimoto K; Tomita H; Suzuki M; Nagano Y; Shibayama K; Arakawa Y; Nagano N
[Ad] Endereço:1​Department of Health and Medical Sciences, Shinshu University Graduate School of Medicine, Nagano, Japan.
[Ti] Título:Genetic shifts in methicillin-resistant Staphylococcus aureus epidemic clones and toxin gene profiles in Japan: comparative analysis among pre-epidemic, epidemic and post-epidemic phases.
[So] Source:J Med Microbiol;67(3):392-399, 2018 Mar.
[Is] ISSN:1473-5644
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:PURPOSE: The decline in methicillin-resistant Staphylococcus aureus (MRSA) isolation rates has become a general observation worldwide, including Japan. We hypothesized that some genetic shift in MRSA might cause this phenomenon, and therefore we investigated the genetic profiles among MRSA clinical isolates obtained from three different epidemic phases in Japan. METHODOLOGY: A total of 353 MRSA isolates were selected from 202 medical facilities in 1990 (pre-epidemic phase), 2004 (epidemic phase) and 2016 (post-epidemic phase). Molecular typing was performed by PCR detection of 22 genes using the polymerase chain reaction (PCR)-based ORF typing (POT) system, including an additional eight genes including small genomic islets and seven toxin genes. RESULTS: Isolates with a POT1 of score 93, identified as presumed clonal complex (pCC)5-staphylococcal cassette chromosome mec (SCCmec) type II including ST5-SCCmec type II New York/Japan clone, represented the major epidemic MRSA lineage in 1990 and 2004. In 2016, however, a marked decrease in isolates with a POT1 score of 93, along with changes in the epidemiology of toxin genes carried, was noted, where the carriers of tst genes including the tst-sec combination were markedly reduced, and those possessing the seb gene alone were markedly increased. Rather, isolates with a POT1 score of 106, including pCC1 or pCC8 among the isolates with SCCmec type IV, which often links to community-associated MRSA, were predominant. Interestingly, the pCC1 and pCC8 lineages were related to sea and tst-sec carriage, respectively. CONCLUSIONS: Over time, a transition in MRSA genetic profiles from a POT1 score of 93 in 1990 and 2004 to 106 in 2014 was found in Japan.
[Mh] Termos MeSH primário: Toxinas Bacterianas/genética
Epidemias
Deriva Genética
Staphylococcus aureus Resistente à Meticilina/genética
Infecções Estafilocócicas/epidemiologia
Infecções Estafilocócicas/microbiologia
[Mh] Termos MeSH secundário: Antibacterianos/farmacologia
Infecção Hospitalar/epidemiologia
Exotoxinas/genética
Seres Humanos
Japão/epidemiologia
Leucocidinas/genética
Meticilina/farmacologia
Resistência a Meticilina/genética
Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos
Staphylococcus aureus Resistente à Meticilina/isolamento & purificação
Testes de Sensibilidade Microbiana
Tipagem Molecular
Fatores de Virulência/genética
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Bacterial Toxins); 0 (Exotoxins); 0 (Leukocidins); 0 (Virulence Factors); Q91FH1328A (Methicillin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180221
[St] Status:MEDLINE
[do] DOI:10.1099/jmm.0.000687


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[PMID]:29458538
[Au] Autor:Ma J; Yu L; Song B; Yu Y; Zhang S; Wei Y; Wu Z; Yao D; Yu W; Zhu Z; Cui Y
[Ad] Endereço:1​College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, PR China.
[Ti] Título:The double adjuvants LTB and CpG significantly enhanced the immuno-protective effects of recombinant GIT derived from Staphylococcus aureus and Streptococcus in mice.
[So] Source:J Med Microbiol;67(3):432-440, 2018 Mar.
[Is] ISSN:1473-5644
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:PURPOSE: In this study, we prepared GapC1-150-IsdB126-361-TRAP (GIT) proteins plus heat-labile enterotoxin B (LTB) as an intra-molecular adjuvant, together with CpG to further enhance its immunogenicity. METHODOLOGY: Initially, the target genes were acquired and inserted into pET-32a (+) vectors to express LTB-GIT protein. LTB-GIT expression was confirmed by Western blotting and its immunocompetence was estimated through ELISA. Further, we immunized BALB/c mice with the LTB-GIT plus CpG adjuvant. After the second immunization, the antigen-specific CD4 cell responses for IFN-γ, IL-2, IL-4 and IL-10 were monitored by intracellular cytokine staining (ICS) assay. After the third immunization, the level of IgG antibodies in the serum from immunized groups was assessed by ELISA, and the protective immune response was appraised by Staphylococcus aureus and Streptococcus dysgalactiae challenge. RESULTS: The ELISA results showed that the OD450nm value of the LTB-GIT group was significantly higher than that of the BSA group. The group immunized with LTB-GIT plus CpG exhibited significantly stronger CD4 T cell responses for IFN-γ, IL-2, IL-4 and IL-10 compared to the group immunized with LTB-GIT, GIT alone orLTB-GIT plus CpG. In addition, the group immunized with LTB-GIT plus CpG generated the highest level of IgG antibodies against GIT among all of the groups, and our results also showed that LTB-GIT plus CpG markedly improved the survival percentage of mice compared to other groups. CONCLUSION: We confirmed that the novel double adjuvants, LTB and CpG, are able to significantly improve GIT-induced immune responses. This formula could be a promising strategy for enhancing the immune efficacy of multi-subunit vaccines against Staphylococcus aureus and streptococcal infection.
[Mh] Termos MeSH primário: Adjuvantes Imunológicos
Toxinas Bacterianas/imunologia
Vacinas Bacterianas/imunologia
Enterotoxinas/imunologia
Oligodesoxirribonucleotídeos/imunologia
Staphylococcus aureus/imunologia
Streptococcus/imunologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Antibacterianos/sangue
Antígenos de Bactérias/imunologia
Proteínas de Bactérias/imunologia
Toxinas Bacterianas/administração & dosagem
Toxinas Bacterianas/genética
Linfócitos T CD4-Positivos
Enterotoxinas/administração & dosagem
Enterotoxinas/genética
Feminino
Interferon gama/imunologia
Interleucina-10/imunologia
Interleucina-2/imunologia
Interleucina-4/imunologia
Camundongos
Camundongos Endogâmicos BALB C
Oligodesoxirribonucleotídeos/genética
Proteínas Recombinantes/genética
Proteínas Recombinantes/imunologia
Infecções Estafilocócicas/imunologia
Staphylococcus aureus/química
Infecções Estreptocócicas/imunologia
Streptococcus/química
Vacinação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adjuvants, Immunologic); 0 (Antibodies, Bacterial); 0 (Antigens, Bacterial); 0 (Bacterial Proteins); 0 (Bacterial Toxins); 0 (Bacterial Vaccines); 0 (CPG-oligonucleotide); 0 (Enterotoxins); 0 (IL10 protein, mouse); 0 (Interleukin-2); 0 (Oligodeoxyribonucleotides); 0 (Recombinant Proteins); 130068-27-8 (Interleukin-10); 207137-56-2 (Interleukin-4); 82115-62-6 (Interferon-gamma)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180221
[St] Status:MEDLINE
[do] DOI:10.1099/jmm.0.000666


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[PMID]:29246991
[Ti] Título: type D enterotoxaemia in cattle, goats and sheep.
[So] Source:Vet Rec;181(24):648-649, 2017 12 16.
[Is] ISSN:2042-7670
[Cp] País de publicação:England
[La] Idioma:eng
[Mh] Termos MeSH primário: Doenças dos Bovinos/diagnóstico
Clostridium perfringens/isolamento & purificação
Enterotoxemia/diagnóstico
Doenças das Cabras/diagnóstico
Doenças dos Ovinos/diagnóstico
[Mh] Termos MeSH secundário: Animais
Toxinas Bacterianas/isolamento & purificação
Bovinos
Doenças dos Bovinos/microbiologia
Clostridium perfringens/classificação
Enterotoxemia/microbiologia
Conteúdo Gastrointestinal
Doenças das Cabras/microbiologia
Cabras
Vigilância de Evento Sentinela/veterinária
Ovinos
Doenças dos Ovinos/microbiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Toxins)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171217
[St] Status:MEDLINE
[do] DOI:10.1136/vr.j5823


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[PMID]:27775159
[Au] Autor:Arévalo MT; Li J; Diaz-Arévalo D; Chen Y; Navarro A; Wu L; Yan Y; Zeng M
[Ad] Endereço:Center of Emphasis in Infectious Diseases, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, USA.
[Ti] Título:A dual purpose universal influenza vaccine candidate confers protective immunity against anthrax.
[So] Source:Immunology;150(3):276-289, 2017 03.
[Is] ISSN:1365-2567
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Preventive influenza vaccines must be reformulated annually because of antigen shift and drift of circulating influenza viral strains. However, seasonal vaccines do not always match the circulating strains, and there is the ever-present threat that avian influenza viruses may adapt to humans. Hence, a universal influenza vaccine is needed to provide protective immunity against a broad range of influenza viruses. We designed an influenza antigen consisting of three tandem M2e repeats plus HA2, in combination with a detoxified anthrax oedema toxin delivery system (EFn plus PA) to enhance immune responses. The EFn-3×M2e-HA2 plus PA vaccine formulation elicited robust, antigen-specific, IgG responses; and was protective against heterologous influenza viral challenge when intranasally delivered to mice three times. Moreover, use of the detoxified anthrax toxin system as an adjuvant had the additional benefit of generating protective immunity against anthrax. Hence, this novel vaccine strategy could potentially address two major emerging public health and biodefence threats.
[Mh] Termos MeSH primário: Adjuvantes Imunológicos/administração & dosagem
Antraz/imunologia
Antígenos de Bactérias/administração & dosagem
Toxinas Bacterianas/administração & dosagem
Vacinas contra Influenza/imunologia
Influenza Humana/imunologia
Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Antibacterianos/sangue
Anticorpos Antivirais/sangue
Bioterrorismo
Células Cultivadas
Citocinas/metabolismo
Seres Humanos
Ativação Linfocitária
Camundongos
Camundongos Endogâmicos BALB C
Infecções por Orthomyxoviridae/imunologia
Linfócitos T/microbiologia
Linfócitos T/virologia
Vacinação
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Adjuvants, Immunologic); 0 (Antibodies, Bacterial); 0 (Antibodies, Viral); 0 (Antigens, Bacterial); 0 (Bacterial Toxins); 0 (Cytokines); 0 (Influenza Vaccines); 0 (anthrax toxin)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE
[do] DOI:10.1111/imm.12683


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[PMID]:29329346
[Au] Autor:Nycz BT; Dominguez SR; Friedman D; Hilden JM; Ir D; Robertson CE; Frank DN
[Ad] Endereço:Division of Adult Infectious Diseases, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
[Ti] Título:Evaluation of bloodstream infections, Clostridium difficile infections, and gut microbiota in pediatric oncology patients.
[So] Source:PLoS One;13(1):e0191232, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Bloodstream infections (BSI) and Clostridium difficile infections (CDI) in pediatric oncology/hematology/bone marrow transplant (BMT) populations are associated with significant morbidity and mortality. The objective of this study was to explore possible associations between altered microbiome composition and the occurrence of BSI and CDI in a cohort of pediatric oncology patients. Stool samples were collected from all patients admitted to the pediatric oncology floor from Oct.-Dec. 2012. Bacterial profiles from patient stools were determined by bacterial 16S rRNA gene profiling. Differences in overall microbiome composition were assessed by a permutation-based multivariate analysis of variance test, while differences in the relative abundances of specific taxa were assessed by Kruskal-Wallis tests. At admission, 9 of 42 patients (21%) were colonized with C. difficile, while 6 of 42 (14%) subsequently developed a CDI. Furthermore, 3 patients (7%) previously had a BSI and 6 patients (14%) subsequently developed a BSI. Differences in overall microbiome composition were significantly associated with disease type (p = 0.0086), chemotherapy treatment (p = 0.018), BSI following admission from any cause (p < 0.0001) or suspected gastrointestinal organisms (p = 0.00043). No differences in baseline microbiota were observed between individuals who did or did not subsequently develop C. difficile infection. Additionally, multiple bacterial groups varied significantly between subjects with post-admission BSI compared with no BSI. Our results suggest that differences in gut microbiota not only are associated with type of cancer and chemotherapy, but may also be predictive of subsequent bloodstream infection.
[Mh] Termos MeSH primário: Bacteriemia/complicações
Infecções por Clostridium/complicações
Microbioma Gastrointestinal
Neoplasias/complicações
Neoplasias/microbiologia
[Mh] Termos MeSH secundário: Adolescente
Bacteriemia/microbiologia
Proteínas de Bactérias/genética
Toxinas Bacterianas/genética
Biodiversidade
Criança
Pré-Escolar
Infecções por Clostridium/microbiologia
Clostridium difficile/genética
Estudos de Coortes
Estudos Transversais
Fezes/microbiologia
Feminino
Microbioma Gastrointestinal/genética
Genes Bacterianos
Seres Humanos
Masculino
Valor Preditivo dos Testes
RNA Bacteriano/genética
RNA Ribossômico 16S/genética
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Bacterial Toxins); 0 (RNA, Bacterial); 0 (RNA, Ribosomal, 16S); 0 (toxB protein, Clostridium difficile)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180113
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191232


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[PMID]:29080422
[Au] Autor:Sakata J; Yonekita T; Kawatsu K
[Ad] Endereço:Division of Microbiology Bacteriology Section, Osaka Institute of Public Health, 3-69, Nakamichi 1-chome, Higashinari-ku, Osaka 537-0025, Japan. Electronic address: sakata@iph.osaka.jp.
[Ti] Título:Development of a rapid immunochromatographic assay to detect contamination of raw oysters with enteropathogenic Vibrio parahaemolyticus.
[So] Source:Int J Food Microbiol;264:16-24, 2018 Jan 02.
[Is] ISSN:1879-3460
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Thermostable direct hemolysin (TDH) and TDH-related hemolysin (TRH) are major virulence factors of enteropathogenic Vibrio parahaemolyticus. TDH and TRH are bacterial exotoxins, and their presence in culture medium serves as a specific marker for detecting this significant pathogen. Here, we developed and evaluated an immunochromatographic assay (TDH/TRH-ICA) to simultaneously or individually detect TDH and TRH. The TDH/TRH-ICA detected TDH in all broth cultures of 47 V. parahaemolyticus strains carrying tdh. The genes encoding TRH are classified as variants trh1 and trh2, and TRH was detected in all broth cultures of 25 V. parahaemolyticus strains carrying trh1 and certain proportion (5/31) of broth cultures of V. parahaemolyticus strains carrying trh2. In contrast, TDH and TRH were not detected in broth cultures of 12 non-enteropathogenic V. parahaemolyticus strains without tdh and trh. It was difficult to detect TRH2 using the TDH/TRH-ICA. However, TRH2 may not serve as a suitable marker for detecting enteropathogenic V. parahaemolyticus, and evidence indicates that TRH2 may not contribute to enteropathogenesis. Further, a screening method using a combination of TDH/TRH-ICA and SPP medium supplemented with 1.5% NaCl (modified-SPP medium) detected oyster samples artificially spiked with 1.1-22 colony-forming units of enteropathogenic V. parahaemolyticus per 25g of oysters within approximately 8.5h, including the enrichment culture. The assay may serve as a method that facilitates the rapid and easy detection of raw oysters contaminated with enteropathogenic V. parahaemolyticus.
[Mh] Termos MeSH primário: Proteínas de Bactérias/análise
Proteínas Hemolisinas/análise
Imunocromatografia/métodos
Ostreidae/microbiologia
Vibrio parahaemolyticus/genética
[Mh] Termos MeSH secundário: Animais
Anticorpos Monoclonais/imunologia
Proteínas de Bactérias/genética
Proteínas de Bactérias/imunologia
Toxinas Bacterianas/análise
Toxinas Bacterianas/genética
Toxinas Bacterianas/imunologia
Proteínas Hemolisinas/genética
Proteínas Hemolisinas/imunologia
Camundongos
Camundongos Endogâmicos BALB C
Vibrio parahaemolyticus/classificação
Vibrio parahaemolyticus/isolamento & purificação
Fatores de Virulência/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Bacterial Proteins); 0 (Bacterial Toxins); 0 (Hemolysin Proteins); 0 (Virulence Factors); 0 (thermostable direct hemolysin-related hemolysin protein, Vibrio parahaemolyticus); 135433-21-5 (thermostable direct hemolysin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171029
[St] Status:MEDLINE


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[PMID]:28449040
[Au] Autor:Yang QE; Walsh TR
[Ad] Endereço:Division of Infection and Immunity, Heath Park Hospital, Cardiff University, Cardiff CF14 4XN, UK.
[Ti] Título:Toxin-antitoxin systems and their role in disseminating and maintaining antimicrobial resistance.
[So] Source:FEMS Microbiol Rev;41(3):343-353, 2017 05 01.
[Is] ISSN:1574-6976
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Toxin-antitoxin systems (TAs) are ubiquitous among bacteria and play a crucial role in the dissemination and evolution of antibiotic resistance, such as maintaining multi-resistant plasmids and inducing persistence formation. Generally, activities of the toxins are neutralised by their conjugate antitoxins. In contrast, antitoxins are more liable to degrade under specific conditions such as stress, and free active toxins interfere with essential cellular processes including replication, translation and cell-wall synthesis. TAs have also been shown to be responsible for plasmid maintenance, stress management, bacterial persistence and biofilm formation. We discuss here the recent findings of these multifaceted TAs (type I-VI) and in particular examine the role of TAs in augmenting the dissemination and maintenance of multi-drug resistance in bacteria.
[Mh] Termos MeSH primário: Bactérias/efeitos dos fármacos
Biofilmes/crescimento & desenvolvimento
Farmacorresistência Bacteriana/fisiologia
Plasmídeos/genética
Sistemas Toxina-Antitoxina/fisiologia
[Mh] Termos MeSH secundário: Antibacterianos/farmacologia
Bactérias/genética
Fenômenos Fisiológicos Bacterianos/genética
Toxinas Bacterianas/metabolismo
Parede Celular/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Bacterial Toxins)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170428
[St] Status:MEDLINE
[do] DOI:10.1093/femsre/fux006


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[PMID]:29305327
[Au] Autor:Moraes ACN; Magalhães VF
[Ad] Endereço:Laboratory of Ecophysiology and Toxicology of Cyanobacteria, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: moraesacn@gmail.com.
[Ti] Título:Renal tubular damage caused by cylindrospermopsin (cyanotoxin) in mice.
[So] Source:Toxicol Lett;286:89-95, 2018 Apr.
[Is] ISSN:1879-3169
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Cylindrospermopsin (CYN) is a cyanotoxin and a hydrophilic alkaloid of 415 Da. The principal effect of CYN is the inhibition of protein synthesis, and it can damage various organs. Studies have demonstrated that the kidney is the most affected organ. CYN has played roles in at least two poisoning cases, i.e., the mysterious Palm Island disease in Australia and the event at Caruaru in Brazil. Therefore, we aimed to determine how CYN disrupts the renal tissue. Dose-response curves following single intraperitoneal injections of purified CYN (at 0, 16, 32, 64 and 128 µg CYN/kg body weight) were created in 10-week-old male BALB/C mice (n = 4). Renal physiology parameters were analyzed after 7 and 14 days. However, no alterations in the glomerular filtration rate (GFR) or nephrin expression (a crucial protein for glomerular integrity) were observed. We detected low-molecular-weight proteinuria and increased excretions of the tubular enzymes lactate dehydrogenase (LDH) and gamma-glutamyl transferase (GGT) at doses of 16, 32 and 64 µg CYN/kg body weight. Furthermore, we observed increases in the renal interstitial space and collagen deposition that indicated edema and fibrosis. The data seem to indicate that the damage is in the proximal tubule.
[Mh] Termos MeSH primário: Toxinas Bacterianas/toxicidade
Nefropatias/induzido quimicamente
Túbulos Renais Proximais/efeitos dos fármacos
Uracila/análogos & derivados
[Mh] Termos MeSH secundário: Animais
Biomarcadores/urina
Colágeno/metabolismo
Relação Dose-Resposta a Droga
Edema/induzido quimicamente
Fibrose
Nefropatias/enzimologia
Nefropatias/patologia
Nefropatias/urina
Túbulos Renais Proximais/enzimologia
L-Lactato Desidrogenase/urina
Masculino
Camundongos Endogâmicos BALB C
Proteinúria/induzido quimicamente
Proteinúria/urina
Medição de Risco
Fatores de Tempo
Uracila/toxicidade
gama-Glutamiltransferase/urina
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Toxins); 0 (Biomarkers); 2JIZ556BA3 (cylindrospermopsin); 56HH86ZVCT (Uracil); 9007-34-5 (Collagen); EC 1.1.1.27 (L-Lactate Dehydrogenase); EC 2.3.2.2 (gamma-Glutamyltransferase)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180107
[St] Status:MEDLINE


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[PMID]:29198864
[Au] Autor:Jiao GS; Kim S; Moayeri M; Thai A; Cregar-Hernandez L; McKasson L; O'Malley S; Leppla SH; Johnson AT
[Ad] Endereço:Hawaii Biotech, 650 Iwilei Road, Suite 204, Honolulu, HI 96817, USA.
[Ti] Título:Small molecule inhibitors of anthrax edema factor.
[So] Source:Bioorg Med Chem Lett;28(2):134-139, 2018 01 15.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Anthrax is a highly lethal disease caused by the Gram-(+) bacteria Bacillus anthracis. Edema toxin (ET) is a major contributor to the pathogenesis of disease in humans exposed to B. anthracis. ET is a bipartite toxin composed of two proteins secreted by the vegetative bacteria, edema factor (EF) and protective antigen (PA). Our work towards identifying a small molecule inhibitor of anthrax edema factor is the subject of this letter. First we demonstrate that the small molecule probe 5'-Fluorosulfonylbenzoyl 5'-adenosine (FSBA) reacts irreversibly with EF and blocks enzymatic activity. We then show that the adenosine portion of FSBA can be replaced to provide more drug-like molecules which are up to 1000-fold more potent against EF relative to FSBA, display low cross reactivity when tested against a panel of kinases, and are nanomolar inhibitors of EF in a cell-based assay of cAMP production.
[Mh] Termos MeSH primário: Antraz/tratamento farmacológico
Bacillus anthracis/efeitos dos fármacos
Toxinas Bacterianas/antagonistas & inibidores
Bibliotecas de Moléculas Pequenas/farmacologia
[Mh] Termos MeSH secundário: Animais
Antígenos de Bactérias/farmacologia
Toxinas Bacterianas/farmacologia
AMP Cíclico/antagonistas & inibidores
AMP Cíclico/biossíntese
Relação Dose-Resposta a Droga
Seres Humanos
Camundongos
Estrutura Molecular
Proteínas Quinases/metabolismo
Células RAW 264.7
Bibliotecas de Moléculas Pequenas/síntese química
Bibliotecas de Moléculas Pequenas/química
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antigens, Bacterial); 0 (Bacterial Toxins); 0 (Small Molecule Libraries); 0 (anthrax toxin); E0399OZS9N (Cyclic AMP); EC 2.7.- (Protein Kinases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171205
[St] Status:MEDLINE


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[PMID]:29293506
[Au] Autor:Choi JE; Nguyen CM; Lee B; Park JH; Oh JY; Choi JS; Kim JC; Song JK
[Ad] Endereço:Research Center for Bio-based Chemistry, Korea Research Institute of Chemical Technology (KRICT), Daejeon, Republic of Korea.
[Ti] Título:Isolation and characterization of a novel metagenomic enzyme capable of degrading bacterial phytotoxin toxoflavin.
[So] Source:PLoS One;13(1):e0183893, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Toxoflavin, a 7-azapteridine phytotoxin produced by the bacterial pathogens such as Burkholderia glumae and Burkholderia gladioli, has been known as one of the key virulence factors in crop diseases. Because the toxoflavin had an antibacterial activity, a metagenomic E. coli clone capable of growing well in the presence of toxoflavin (30 µg/ml) was isolated and the first metagenome-derived toxoflavin-degrading enzyme, TxeA of 140 amino acid residues, was identified from the positive E. coli clone. The conserved amino acids for metal-binding and extradiol dioxygenase activity, Glu-12, His-8 and Glu-130, were revealed by the sequence analysis of TxeA. The optimum conditions for toxoflavin degradation were evaluated with the TxeA purified in E. coli. Toxoflavin was totally degraded at an initial toxoflavin concentration of 100 µg/ml and at pH 5.0 in the presence of Mn2+, dithiothreitol and oxygen. The final degradation products of toxoflavin and methyltoxoflavin were fully identified by MS and NMR as triazines. Therefore, we suggested that the new metagenomic enzyme, TxeA, provided the clue to applying the new metagenomic enzyme to resistance development of crop plants to toxoflavin-mediated disease as well as to biocatalysis for Baeyer-Villiger type oxidation.
[Mh] Termos MeSH primário: Toxinas Bacterianas/metabolismo
Burkholderia/metabolismo
Enzimas/metabolismo
Metagenômica
Pirimidinonas/metabolismo
Triazinas/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Homologia de Sequência de Aminoácidos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Bacterial Toxins); 0 (Enzymes); 0 (Pyrimidinones); 0 (Triazines); 5N5YI4IP1P (toxoflavin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180103
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183893



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