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[PMID]:28470446
[Au] Autor:Sundaran PS; Bhaskaran A; Alex ST; Prasad T; Haritha VH; Anie Y; Kumary TV; Anil Kumar PR
[Ad] Endereço:Division of Tissue Culture, Department of Applied Biology, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, 695 012, India.
[Ti] Título:Drug loaded microbeads entrapped electrospun mat for wound dressing application.
[So] Source:J Mater Sci Mater Med;28(6):88, 2017 Jun.
[Is] ISSN:1573-4838
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A new design of antibiotic loaded wound dressing and its initial in vitro evaluation is described. Chitosan microbeads loaded with ampicillin were sandwiched within polycaprolactone electrospun mat (MbAPPCL). The morphology was analyzed by scanning electron microscopy and surface chemistry was characterized by Fourier Transform Infrared Spectroscopy. In vitro cytotoxicity using L-929 fibroblast cells by direct contact test and elution assay revealed non-cytotoxic nature of MbAPPCL. The cell adhesion and viability analysis further confirmed the cytocompatibility of MbAPPCL as a wound dressing material. Percentage hemolysis and platelet adhesion on the mat exposed to blood substantiated the hemocompatibility. The antibiotic susceptibility test analyzed on Staphylococcus aureus by agar plate method confirmed the drug release and antimicrobial property. The proposed wound dressing model explained with ampicillin as a candidate drug has the potential to include microbeads with different antibiotics for multi drug treatment.
[Mh] Termos MeSH primário: Bandagens
Portadores de Fármacos
Microesferas
[Mh] Termos MeSH secundário: Animais
Antibacterianos/química
Antibacterianos/farmacologia
Materiais Biocompatíveis
Plaquetas
Linhagem Celular
Quitosana
Técnicas Eletroquímicas
Fibroblastos/fisiologia
Teste de Materiais
Camundongos
Penicilinas/química
Penicilinas/farmacologia
Staphylococcus aureus/efeitos dos fármacos
Estreptomicina/química
Estreptomicina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Biocompatible Materials); 0 (Drug Carriers); 0 (Penicillins); 9012-76-4 (Chitosan); Y45QSO73OB (Streptomycin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1007/s10856-017-5893-8


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[PMID]:29458686
[Au] Autor:Anson LW; Chau K; Sanderson N; Hoosdally S; Bradley P; Iqbal Z; Phan H; Foster D; Oakley S; Morgan M; Peto TEA; Modernizing Medical Microbiology Informatics Group Mmmig; Crook DW; Pankhurst LJ
[Ad] Endereço:1​Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
[Ti] Título:DNA extraction from primary liquid blood cultures for bloodstream infection diagnosis using whole genome sequencing.
[So] Source:J Med Microbiol;67(3):347-357, 2018 Mar.
[Is] ISSN:1473-5644
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Speed of bloodstream infection diagnosis is vital to reduce morbidity and mortality. Whole genome sequencing (WGS) performed directly from liquid blood culture could provide single-assay species and antibiotic susceptibility prediction; however, high inhibitor and human cell/DNA concentrations limit pathogen recovery. We develop a method for the preparation of bacterial DNA for WGS-based diagnostics direct from liquid blood culture. METHODOLOGY: We evaluate three commercial DNA extraction kits: BiOstic Bacteraemia, Amplex Hyplex and MolYsis Plus. Differential centrifugation, filtration, selective lysis and solid-phase reversible immobilization bead clean-up are tested to improve human cells/DNA and inhibitor removal. Using WGS (Illumina/MinION), we assess human DNA removal, pathogen recovery, and predict species and antibiotic susceptibility inpositive blood cultures of 44 Gram-negative and 54 Staphylococcus species.Results/Key findings. BiOstic kit extractions yield the greatest mean DNA concentration, 94-301 ng µl , versus 0-2.5 ng µl using Amplex and MolYsis kits. However, we note higher levels of inhibition (260/280 ratio 0.9-2.1) and human DNA (0.0-4.4×10 copies) in BiOstic extracts. Differential centrifugation (2000 g, 1 min) prior to BiOstic extraction reduces human DNA by 63-89 % with selective lysis minimizing by a further 62 %. Post-extraction bead clean-up lowers inhibition. Overall, 67 % of sequenced samples (Illumina MiSeq) contain <10 % human DNA, with >93 % concordance between WGS-based species and susceptibility predictions and clinical diagnosis. If >60 % of sequencing reads are human (7/98 samples) susceptibility prediction becomes compromised. Novel MinION-based WGS (n=9) currently gives rapid species identification but not susceptibility prediction. CONCLUSION: Our method for DNA preparation allows WGS-based diagnosis direct from blood culture bottles, providing species and antibiotic susceptibility prediction in a single assay.
[Mh] Termos MeSH primário: Bacteriemia/diagnóstico
Hemocultura
DNA Bacteriano/isolamento & purificação
Genoma Bacteriano
Sequenciamento Completo do Genoma
[Mh] Termos MeSH secundário: Bacteriemia/microbiologia
Infecções Relacionadas a Cateter/diagnóstico
Infecções Relacionadas a Cateter/microbiologia
DNA Bacteriano/análise
DNA Bacteriano/genética
Escherichia coli/genética
Seres Humanos
Testes de Sensibilidade Microbiana
Técnicas de Diagnóstico Molecular/métodos
Kit de Reagentes para Diagnóstico
Análise de Sequência de DNA/métodos
Staphylococcus aureus/genética
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Bacterial); 0 (Reagent Kits, Diagnostic)
[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.0.000664


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[PMID]:29458674
[Au] Autor:Nair S; Poonacha N; Desai S; Hiremath D; Tuppad D; Mohan T; Chikkamadaiah R; Durgaiah M; Kumar S; Channabasappa S; Vipra A; Sharma U
[Ad] Endereço:GangaGen Biotechnologies Pvt Ltd., Bangalore, India.
[Ti] Título:Restoration of sensitivity of a diverse set of drug-resistant Staphylococcus clinical strains by bactericidal protein P128.
[So] Source:J Med Microbiol;67(3):296-307, 2018 Mar.
[Is] ISSN:1473-5644
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:PURPOSE: P128, a phage-derived lysin, exerts antibacterial activity on staphylococci by cleaving the pentaglycine-bridge of peptidoglycan. We sought to determine whether the presence of P128 could re-sensitize drug-resistant bacteria to antibiotics by virtue of its cell wall degrading property. METHODOLOGY: P128 was tested in combination with standard-of-care (SoC) drugs by chequerboard assays on planktonic cells and biofilms of strains individually resistant to these drugs. The bactericidal effect of P128 and drug combinations on planktonic cells and biofilms was measured by c.f.u. reduction assays. A mouse model of MRSA bacteraemia was used to test the efficacy of P128 and oxacillin in combination. RESULTS: A combination of sub-MIC P128 (0.025-0.20 µg ml ) and 0.5 µg ml of oxacillin resulted in inhibition of bacterial growth in four MRSA strains. Similar results were seen with all the other drugs tested, wherein sub-MIC of P128 re-sensitized S. aureus and CoNS strains to SoC drugs. The chequerboard assays on strains of S. aureus and CoNS showed that combinations of P128 and antibiotics consistently inhibited bacterial growth on biofilms. Data from scanning electron microscopy and c.f.u. reduction assays on drug-resistant S. aureus and CoNS demonstrated that sub-MICs of P128 and SoC antibiotics could kill biofilm-embedded bacteria. In vivo, a combination of sub-therapeutic doses of P128 and oxacillin could help protect animals from fatal bacteraemia. CONCLUSION: The ability of P128 to re-sensitize bacteria to SoC drugs suggests that combinations of P128 and SoC antibiotics can potentially be developed to treat infections caused by drug-resistant strains of staphylococci.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Farmacorresistência Bacteriana/efeitos dos fármacos
Proteínas Recombinantes de Fusão/farmacologia
Staphylococcus aureus/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Biofilmes/efeitos dos fármacos
Biofilmes/crescimento & desenvolvimento
Modelos Animais de Doenças
Seres Humanos
Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos
Camundongos
Testes de Sensibilidade Microbiana
Oxacilina/farmacologia
Proteínas Recombinantes de Fusão/metabolismo
Infecções Estafilocócicas/microbiologia
Staphylococcus aureus/crescimento & desenvolvimento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (P128 antistaphylococcal chimeric protein); 0 (Recombinant Fusion Proteins); UH95VD7V76 (Oxacillin)
[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.0.000697


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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]:29458526
[Au] Autor:Ma J; Wei Y; Zhang L; Wang X; Yao D; Liu D; Liu W; Yu S; Yu Y; Wu Z; Yu L; Zhu Z; Cui Y
[Ad] Endereço:College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing 163319, PR China.
[Ti] Título:Identification of a novel linear B-cell epitope as a vaccine candidate in the N2N3 subdomain of Staphylococcus aureus fibronectin-binding protein A.
[So] Source:J Med Microbiol;67(3):423-431, 2018 Mar.
[Is] ISSN:1473-5644
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:PURPOSE: To explore an epitope-based vaccine against Staphylococcus aureus, we screened the epitopes in the N2N3 subdomain of fibronectin-binding protein A (FnBPA) as a surface component of S. aureus. METHODOLOGY: We expressed N2N3 proteins and prepared monoclonal antibodies (mAbs) against N2N3 by the hybridoma technique, before screening the B-cell epitopes in N2N3 using a phage-displayed random 12-mer peptide library with these mAbs against N2N3. Finally, we analysed the characters of the screened epitopes using immunofluorescence and an S. aureus infection assay. RESULTS: In this paper, we identified a linear B-cell epitope in N2N3 through screening a phage-displayed peptide library with a 3C3 mAb against the N2N3. The 3C3 mAb recognized the 159IETFNKANNRFSH171 sequence of the N2N3 subdomain. Subsequently, site-directed mutagenic analysis demonstrated that residues F162, K164, N167, R168 and F169 formed the core of 159IETFNKANNRFSH171, and this core motif was the minimal determinant of the B-cell epitope recognized by the 3C3 mAb. The epitope 159IETFNKANNRFSH171 showed high homology among different S. aureus strains. Moreover, this epitope was exposed on the surface of the S. aureus by using an enzyme-linked immunosorbent assay (ELISA) assay and an indirect immunofluorescence assay. As expected, the epitope peptide evoked a protective immune response against S. aureus infection in immunized mice. CONCLUSION: We identified a novel linear B-cell epitope, 159IETFNKANNRFSH171, in the N2N3 subdomain of S. aureus fibronectin-binding protein A that is recognized by 3C3 mAb, which will contribute to the further study of an epitope-based vaccine candidate against S. aureus.
[Mh] Termos MeSH primário: Adesinas Bacterianas/imunologia
Epitopos de Linfócito B/imunologia
Infecções Estafilocócicas/prevenção & controle
Vacinas Antiestafilocócicas/imunologia
Staphylococcus aureus/imunologia
[Mh] Termos MeSH secundário: Adesinas Bacterianas/química
Adesinas Bacterianas/genética
Animais
Anticorpos Monoclonais/imunologia
Anticorpos Monoclonais/isolamento & purificação
Ensaio de Imunoadsorção Enzimática
Mapeamento de Epitopos
Epitopos de Linfócito B/química
Epitopos de Linfócito B/genética
Imunização
Camundongos
Biblioteca de Peptídeos
Ligação Proteica
Infecções Estafilocócicas/imunologia
Staphylococcus aureus/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adhesins, Bacterial); 0 (Antibodies, Monoclonal); 0 (Epitopes, B-Lymphocyte); 0 (Peptide Library); 0 (Staphylococcal Vaccines); 0 (fibronectin-binding proteins, bacterial)
[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.0.000633


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[PMID]:29442030
[Au] Autor:Resende AFC; Pereira AF; Moreira TP; Patrício PSO; Fialho SL; Cunha GMF; Silva-Cunha A; Magalhães JT; Silva GR
[Ti] Título:PLGA Implants containing vancomycin and dexamethasone: development, characterization and bactericidal effects.
[So] Source:Pharmazie;71(8):439-446, 2016 08 01.
[Is] ISSN:0031-7144
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Post-operative endophthalmitis is an infection and an inflammation of the eye following a surgical procedure. Its treatment is based on drug injections into the eye. However, this treatment can lead to ocular complications. Intraocular implants could substitute the conventional therapy. Poly(lactic-co-glycolic acid) (PLGA) implants comprising on vancomycin and dexamethasone were evaluated as drug delivery system to treat endophthalmitis after cataract surgery. Implants were characterized by drug content uniformity, Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), Wide Angle X-ray Scattering (WAXS), Scanning Electron Microscopy (SEM) and in vitro drug release. The bactericidal effect of vancomycin, eluted from the implants, was demonstrated against Staphylococcus aureus and Staphylococcus epidermidis. The drugs were uniformly distributed in the polymer. The analytical techniques revealed the chemical integrity of the drugs incorporated into the polymer and the modification of dexamethasone semi-crystalline nature. Drugs were controlled released from implants; and the eluted vancomycin showed bactericidal effects. In conclusion, PLGA implants containing vancomycin and dexamethasone may represent a therapeutic alternative to treat post-operative endophthalmitis.
[Mh] Termos MeSH primário: Antibacterianos/administração & dosagem
Antibacterianos/uso terapêutico
Anti-Inflamatórios/administração & dosagem
Anti-Inflamatórios/uso terapêutico
Bactérias/efeitos dos fármacos
Dexametasona/administração & dosagem
Dexametasona/uso terapêutico
Portadores de Fármacos
Ácido Láctico
Ácido Poliglicólico
Infecção da Ferida Cirúrgica/prevenção & controle
Vancomicina/administração & dosagem
Vancomicina/uso terapêutico
[Mh] Termos MeSH secundário: Antibacterianos/farmacologia
Implantes de Medicamento
Liberação Controlada de Fármacos
Endoftalmite/microbiologia
Endoftalmite/prevenção & controle
Seres Humanos
Testes de Sensibilidade Microbiana
Procedimentos Cirúrgicos Oftalmológicos
Staphylococcus aureus/efeitos dos fármacos
Staphylococcus epidermidis/efeitos dos fármacos
Vancomicina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Anti-Inflammatory Agents); 0 (Drug Carriers); 0 (Drug Implants); 0 (polylactic acid-polyglycolic acid copolymer); 26009-03-0 (Polyglycolic Acid); 33X04XA5AT (Lactic Acid); 6Q205EH1VU (Vancomycin); 7S5I7G3JQL (Dexamethasone)
[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:180215
[St] Status:MEDLINE
[do] DOI:10.1691/ph.2016.6009


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[PMID]:29295973
[Au] Autor:Blaskovich MAT; Hansford KA; Gong Y; Butler MS; Muldoon C; Huang JX; Ramu S; Silva AB; Cheng M; Kavanagh AM; Ziora Z; Premraj R; Lindahl F; Bradford TA; Lee JC; Karoli T; Pelingon R; Edwards DJ; Amado M; Elliott AG; Phetsang W; Daud NH; Deecke JE; Sidjabat HE; Ramaologa S; Zuegg J; Betley JR; Beevers APG; Smith RAG; Roberts JA; Paterson DL; Cooper MA
[Ad] Endereço:Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD, 4072, Australia. m.blaskovich@uq.edu.au.
[Ti] Título:Protein-inspired antibiotics active against vancomycin- and daptomycin-resistant bacteria.
[So] Source:Nat Commun;9(1):22, 2018 01 02.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The public health threat posed by a looming 'post-antibiotic' era necessitates new approaches to antibiotic discovery. Drug development has typically avoided exploitation of membrane-binding properties, in contrast to nature's control of biological pathways via modulation of membrane-associated proteins and membrane lipid composition. Here, we describe the rejuvenation of the glycopeptide antibiotic vancomycin via selective targeting of bacterial membranes. Peptide libraries based on positively charged electrostatic effector sequences are ligated to N-terminal lipophilic membrane-insertive elements and then conjugated to vancomycin. These modified lipoglycopeptides, the 'vancapticins', possess enhanced membrane affinity and activity against methicillin-resistant Staphylococcus aureus (MRSA) and other Gram-positive bacteria, and retain activity against glycopeptide-resistant strains. Optimised antibiotics show in vivo efficacy in multiple models of bacterial infection. This membrane-targeting strategy has potential to 'revitalise' antibiotics that have lost effectiveness against recalcitrant bacteria, or enhance the activity of other intravenous-administered drugs that target membrane-associated receptors.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Bactérias/efeitos dos fármacos
Daptomicina/farmacologia
Farmacorresistência Bacteriana/efeitos dos fármacos
Proteínas de Membrana/metabolismo
Vancomicina/farmacologia
[Mh] Termos MeSH secundário: Animais
Antibacterianos/metabolismo
Antibacterianos/farmacocinética
Bactérias/classificação
Sobrevivência Celular/efeitos dos fármacos
Glicopeptídeos/metabolismo
Células HEK293
Células Hep G2
Seres Humanos
Masculino
Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos
Camundongos
Testes de Sensibilidade Microbiana
Viabilidade Microbiana/efeitos dos fármacos
Staphylococcus aureus/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Glycopeptides); 0 (Membrane Proteins); 6Q205EH1VU (Vancomycin); NWQ5N31VKK (Daptomycin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180104
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02123-w


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[PMID]:28456664
[Au] Autor:Fujita J; Harada R; Maeda Y; Saito Y; Mizohata E; Inoue T; Shigeta Y; Matsumura H
[Ad] Endereço:Department of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
[Ti] Título:Identification of the key interactions in structural transition pathway of FtsZ from Staphylococcus aureus.
[So] Source:J Struct Biol;198(2):65-73, 2017 May.
[Is] ISSN:1095-8657
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The tubulin-homolog protein FtsZ is essential for bacterial cell division. FtsZ polymerizes to form protofilaments that assemble into a contractile ring-shaped structure in the presence of GTP. Recent studies showed that FtsZ treadmilling coupled with the GTPase activity drives cell wall synthesis and bacterial cell division. The treadmilling caused by assembly and disassembly of FtsZ links to a conformational change of the monomer from a tense (T) to a relaxed (R) state, but considerable controversy still remains concerning the mechanism. In this study, we report crystal structures of FtsZ from Staphylococcus aureus corresponding to the T and R state conformations in the same crystal, indicating the structural equilibrium of the two state. The two structures identified a key residue Arg29, whose importance was also confirmed by our modified MD simulations. Crystal structures of the R29A mutant showed T and R state-like conformations with slight but important structural changes compared to those of wild-type. Collectively, these data provide new insights for understanding how intramolecular interactions are related to the structural transition of FtsZ.
[Mh] Termos MeSH primário: Proteínas de Bactérias/química
Proteínas do Citoesqueleto/química
Mutação de Sentido Incorreto
Staphylococcus aureus/química
[Mh] Termos MeSH secundário: Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Cristalografia por Raios X
Proteínas do Citoesqueleto/genética
Proteínas do Citoesqueleto/metabolismo
Conformação Proteica
Staphylococcus aureus/genética
Staphylococcus aureus/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Cytoskeletal Proteins); 0 (FtsZ protein, Bacteria)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE


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[PMID]:28465342
[Au] Autor:Stefanova D; Raychev A; Arezes J; Ruchala P; Gabayan V; Skurnik M; Dillon BJ; Horwitz MA; Ganz T; Bulut Y; Nemeth E
[Ad] Endereço:Molecular, Cellular, and Integrative Physiology Graduate Program and.
[Ti] Título:Endogenous hepcidin and its agonist mediate resistance to selected infections by clearing non-transferrin-bound iron.
[So] Source:Blood;130(3):245-257, 2017 07 20.
[Is] ISSN:1528-0020
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The iron-regulatory hormone hepcidin is induced early in infection, causing iron sequestration in macrophages and decreased plasma iron; this is proposed to limit the replication of extracellular microbes, but could also promote infection with macrophage-tropic pathogens. The mechanisms by which hepcidin and hypoferremia modulate host defense, and the spectrum of microbes affected, are poorly understood. Using mouse models, we show that hepcidin was selectively protective against siderophilic extracellular pathogens ( O9) by controlling non-transferrin-bound iron (NTBI) rather than iron-transferrin concentration. NTBI promoted the rapid growth of siderophilic but not nonsiderophilic bacteria in mice with either genetic or iatrogenic iron overload and in human plasma. Hepcidin or iron loading did not affect other key components of innate immunity, did not indiscriminately promote intracellular infections ( ), and had no effect on extracellular nonsiderophilic O8 or Hepcidin analogs may be useful for treatment of siderophilic infections.
[Mh] Termos MeSH primário: Infecções Relacionadas a Cateter/imunologia
Hemocromatose/imunologia
Hepcidinas/imunologia
Sobrecarga de Ferro/imunologia
Ferro/metabolismo
Infecções Estafilocócicas/imunologia
[Mh] Termos MeSH secundário: Animais
Ligação Competitiva
Infecções Relacionadas a Cateter/metabolismo
Infecções Relacionadas a Cateter/microbiologia
Infecções Relacionadas a Cateter/mortalidade
Modelos Animais de Doenças
Resistência à Doença
Expressão Gênica
Hemocromatose/metabolismo
Hemocromatose/microbiologia
Hemocromatose/mortalidade
Hepcidinas/agonistas
Hepcidinas/deficiência
Hepcidinas/genética
Seres Humanos
Ferro/imunologia
Sobrecarga de Ferro/metabolismo
Sobrecarga de Ferro/microbiologia
Sobrecarga de Ferro/mortalidade
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Mycobacterium tuberculosis/efeitos dos fármacos
Mycobacterium tuberculosis/crescimento & desenvolvimento
Mycobacterium tuberculosis/metabolismo
Oligopeptídeos/farmacologia
Ligação Proteica
Infecções Estafilocócicas/metabolismo
Infecções Estafilocócicas/microbiologia
Infecções Estafilocócicas/mortalidade
Staphylococcus aureus
Análise de Sobrevida
Transferrina/genética
Transferrina/metabolismo
Yersinia enterocolitica/efeitos dos fármacos
Yersinia enterocolitica/crescimento & desenvolvimento
Yersinia enterocolitica/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Hamp1 protein, mouse); 0 (Hepcidins); 0 (Oligopeptides); 0 (Transferrin); E1UOL152H7 (Iron)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1182/blood-2017-03-772715


  10 / 52195 MEDLINE  
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[PMID]:29353723
[Au] Autor:Wu YZ; Zhang HW; Sun ZH; Dai JG; Hu YC; Li R; Lin PC; Xia GY; Wang LY; Qiu BL; Zhang JF; Ge GB; Lin S
[Ad] Endereço:State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
[Ti] Título:Bysspectin A, an unusual octaketide dimer and the precursor derivatives from the endophytic fungus Byssochlamys spectabilis IMM0002 and their biological activities.
[So] Source:Eur J Med Chem;145:717-725, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Bysspectin A (1), a polyketide-derived octaketide dimer with a novel carbon skeleton, and two new precursor derivatives, bysspectins B and C (2 and 3), were obtained from an organic extract of the endophytic fungus Byssochlamys spectabilis that had been isolated from a leaf tissue of the traditional Chinese medicinal plant Edgeworthia chrysantha, together with a known octaketide, paecilocin A (4). Their structures were determined by HRMS, 1D and 2D NMR spectroscopic analysis. A plausible route for their biosynthetic pathway is proposed. Compounds 1-3 were tested for their antimicrobial activities. Only compound 3 was weakly active against Escherichia coli and Staphyloccocus aureus with MIC values of 32 and 64 µg/mL, respectively. Further, the inhibitory effects on human carboxylesterases (hCE1, hCE2) of compounds 1 and 4 were evaluated. The results demonstrated that bysspectin A (1) was a novel and highly selective inhibitor against hCE2 with the IC value of 2.01 µM. Docking simulation also demonstrated that active compound 1 created interaction with the Ser-288 (the catalytic amino-acid in the catalytic cavity) of hCE2 via hydrogen bonding, revealing its highly selective inhibition toward hCE2.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Byssochlamys/química
Carboxilesterase/antagonistas & inibidores
Hidrolases de Éster Carboxílico/antagonistas & inibidores
Inibidores Enzimáticos/farmacologia
Escherichia coli/efeitos dos fármacos
Policetídeos/farmacologia
Staphylococcus aureus/efeitos dos fármacos
[Mh] Termos MeSH secundário: Antibacterianos/química
Antibacterianos/isolamento & purificação
Biocatálise
Carboxilesterase/metabolismo
Hidrolases de Éster Carboxílico/metabolismo
Dimerização
Relação Dose-Resposta a Droga
Inibidores Enzimáticos/química
Inibidores Enzimáticos/isolamento & purificação
Seres Humanos
Testes de Sensibilidade Microbiana
Simulação de Acoplamento Molecular
Estrutura Molecular
Policetídeos/química
Policetídeos/isolamento & purificação
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Enzyme Inhibitors); 0 (Polyketides); 0 (bysspectin A); EC 3.1.1.- (Carboxylic Ester Hydrolases); EC 3.1.1.1 (CES1 protein, human); EC 3.1.1.1 (CES2 protein, human); EC 3.1.1.1 (Carboxylesterase)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180123
[St] Status:MEDLINE



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