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  1 / 1021 MEDLINE  
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[PMID]:29458676
[Au] Autor:Gorla MC; Cassiolato AP; Pinhata JMW; de Moraes C; Corso A; Gagetti P; Lemos AP
[Ad] Endereço:1​Bacteriology Department, Adolfo Lutz Institute, Av. Dr. Arnaldo 351, São Paulo, CEP 01246-902, SP, Brazil.
[Ti] Título:Emergence of resistance to ciprofloxacin in Neisseria meningitidis in Brazil.
[So] Source:J Med Microbiol;67(3):286-288, 2018 Mar.
[Is] ISSN:1473-5644
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:To prevent secondary invasive meningococcal disease (IMD) cases and outbreaks, antimicrobial prophylaxis of high-risk contacts is indicated. This study reports two ciprofloxacin-resistant Neisseria meningitidis strains in Brazil. The 3523 N. meningitidis isolates collected throughout Brazil from 2009 to 2016 were evaluated for antimicrobial resistance. Meningococcal isolates showing minimal inhibitory concentrations, MICs≥0.125µg ml to ciprofloxacin, were analysed to determine the presence of mutations in the quinolone resistance-determining regions (QRDRs) of gyrA and parC genes. Two ciprofloxacin-resistant N. meningitidis isolates were found, both presenting a single mutation in the quinolone resistance-determining region of the gyrA gene. These results confirmed that ciprofloxacin is still a first-line drug for chemoprophylaxis. However, we highlight the importance of continued surveillance to monitor the trends of N. meningitidis susceptibility profiles to the antimicrobials recommended for chemoprophylaxis and IMD treatment.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Ciprofloxacino/farmacologia
Farmacorresistência Bacteriana/genética
Infecções Meningocócicas/microbiologia
Neisseria meningitidis/efeitos dos fármacos
Neisseria meningitidis/genética
[Mh] Termos MeSH secundário: Brasil/epidemiologia
DNA Girase/genética
DNA Topoisomerase IV/genética
Fluoroquinolonas/farmacologia
Seres Humanos
Infecções Meningocócicas/epidemiologia
Testes de Sensibilidade Microbiana
Tipagem de Sequências Multilocus
Mutação
Neisseria gonorrhoeae/isolamento & purificação
Quinolonas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Fluoroquinolones); 0 (Quinolones); 5E8K9I0O4U (Ciprofloxacin); EC 5.99.1.- (DNA Topoisomerase IV); EC 5.99.1.3 (DNA Gyrase)
[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.0.000685


  2 / 1021 MEDLINE  
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[PMID]:28453633
[Au] Autor:Ehrmann E; Jolivet-Gougeon A; Bonnaure-Mallet M; Fosse T
[Ad] Endereço:Pôle odontologie, CHU de Nice, Nice, France.
[Ti] Título:Role of DNA gyrase and topoisomerase IV mutations in fluoroquinolone resistance of Capnocytophaga spp. clinical isolates and laboratory mutants.
[So] Source:J Antimicrob Chemother;72(8):2208-2212, 2017 Aug 01.
[Is] ISSN:1460-2091
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Objectives: Capnocytophaga spp. are often reported to cause bacteraemia and extra-oral infections and are characterized by their significant contribution to resistance to ß-lactam and macrolide-lincosamide-streptogramin antibiotics in the human oral microbiota. The implication of mutations in the quinolone resistance-determining region (QRDR) of DNA gyrase A and B ( gyrA and gyrB ) and topoisomerase IV ( parC and parE ) of fluoroquinolone (FQ)-resistant Capnocytophaga spp., hitherto unknown, was explored in this study. Methods: Two reference strains ( Capnocytophaga gingivalis ATCC 33624 and Capnocytophaga sputigena ATCC 33612) and four Capnocytophaga spp. isolated from clinical samples were studied. Nine in vitro FQ-resistant mutants, derived from two reference strains and one FQ-susceptible clinical isolate, were selected by successive inoculations onto medium containing levofloxacin. MICs of ofloxacin, norfloxacin, ciprofloxacin, levofloxacin and moxifloxacin were determined. The presumed QRDRs of GyrA, GyrB, ParC and ParE from Capnocytophaga spp. were determined by sequence homology to Bacteroides fragilis and Escherichia coli . PCR primers were designed to amplify the presumed QRDR genetic region of Capnocytophaga spp. and sequence analyses were performed using the BLAST program at the National Center for Biotechnology Information. Results and conclusions: gyrA mutations leading to a substitution from amino acid position 80 to 86 were systematically detected in Capnocytophaga spp. with ciprofloxacin MIC >1 mg/L and considered as the primary target of FQs. No mutational alteration in the QRDR of gyrB was detected. Other mutations in parC and parE led to spontaneous amino acid substitutions of DNA topoisomerase IV subunit B with no alteration in FQ susceptibility.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Capnocytophaga/efeitos dos fármacos
Capnocytophaga/enzimologia
DNA Girase/genética
DNA Topoisomerase IV/genética
Fluoroquinolonas/farmacologia
Mutação de Sentido Incorreto
[Mh] Termos MeSH secundário: Substituição de Aminoácidos
Capnocytophaga/genética
Capnocytophaga/isolamento & purificação
Infecções por Bactérias Gram-Negativas/microbiologia
Seres Humanos
Testes de Sensibilidade Microbiana
Reação em Cadeia da Polimerase
Análise de Sequência de DNA
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Fluoroquinolones); EC 5.99.1.- (DNA Topoisomerase IV); EC 5.99.1.3 (DNA Gyrase)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1093/jac/dkx119


  3 / 1021 MEDLINE  
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[PMID]:29016650
[Au] Autor:Ivanov SM; Cawley A; Huber RG; Bond PJ; Warwicker J
[Ad] Endereço:Manchester Institute of Biotechnology, School of Chemistry, The University of Manchester, Manchester, United Kingdom.
[Ti] Título:Protein-protein interactions in paralogues: Electrostatics modulates specificity on a conserved steric scaffold.
[So] Source:PLoS One;12(10):e0185928, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:An improved knowledge of protein-protein interactions is essential for better understanding of metabolic and signaling networks, and cellular function. Progress tends to be based on structure determination and predictions using known structures, along with computational methods based on evolutionary information or detailed atomistic descriptions. We hypothesized that for the case of interactions across a common interface, between proteins from a pair of paralogue families or within a family of paralogues, a relatively simple interface description could distinguish between binding and non-binding pairs. Using binding data for several systems, and large-scale comparative modeling based on known template complex structures, it is found that charge-charge interactions (for groups bearing net charge) are generally a better discriminant than buried non-polar surface. This is particularly the case for paralogue families that are less divergent, with more reliable comparative modeling. We suggest that electrostatic interactions are major determinants of specificity in such systems, an observation that could be used to predict binding partners.
[Mh] Termos MeSH primário: Toxinas Bacterianas/química
Sequência Conservada
Eletricidade Estática
Enzimas de Conjugação de Ubiquitina/química
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Aminoácidos
Bactérias/química
Bactérias/metabolismo
Proteínas de Bactérias/química
Proteínas de Bactérias/metabolismo
Toxinas Bacterianas/metabolismo
Sítios de Ligação
DNA Topoisomerase IV/química
DNA Topoisomerase IV/metabolismo
Proteínas de Ligação a DNA/química
Proteínas de Ligação a DNA/metabolismo
Seres Humanos
Interações Hidrofóbicas e Hidrofílicas
Cinética
Glicoproteínas de Membrana/química
Glicoproteínas de Membrana/metabolismo
Ligação Proteica
Conformação Proteica em alfa-Hélice
Domínios e Motivos de Interação entre Proteínas
Alinhamento de Sequência
Homologia de Sequência de Aminoácidos
Termodinâmica
Enzimas de Conjugação de Ubiquitina/metabolismo
Ubiquitina-Proteína Ligases/química
Ubiquitina-Proteína Ligases/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acids); 0 (Bacterial Proteins); 0 (Bacterial Toxins); 0 (DNA-Binding Proteins); 0 (Membrane Glycoproteins); 0 (parD protein, Bacteria); 147571-32-2 (VapB protein, Bacteria); EC 2.3.2.23 (Ubiquitin-Conjugating Enzymes); EC 2.3.2.27 (Ubiquitin-Protein Ligases); EC 5.99.1.- (DNA Topoisomerase IV)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171011
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0185928


  4 / 1021 MEDLINE  
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[PMID]:28934496
[Au] Autor:Ashley RE; Dittmore A; McPherson SA; Turnbough CL; Neuman KC; Osheroff N
[Ad] Endereço:Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA.
[Ti] Título:Activities of gyrase and topoisomerase IV on positively supercoiled DNA.
[So] Source:Nucleic Acids Res;45(16):9611-9624, 2017 Sep 19.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Although bacterial gyrase and topoisomerase IV have critical interactions with positively supercoiled DNA, little is known about the actions of these enzymes on overwound substrates. Therefore, the abilities of Bacillus anthracis and Escherichia coli gyrase and topoisomerase IV to relax and cleave positively supercoiled DNA were analyzed. Gyrase removed positive supercoils ∼10-fold more rapidly and more processively than it introduced negative supercoils into relaxed DNA. In time-resolved single-molecule measurements, gyrase relaxed overwound DNA with burst rates of ∼100 supercoils per second (average burst size was 6.2 supercoils). Efficient positive supercoil removal required the GyrA-box, which is necessary for DNA wrapping. Topoisomerase IV also was able to distinguish DNA geometry during strand passage and relaxed positively supercoiled substrates ∼3-fold faster than negatively supercoiled molecules. Gyrase maintained lower levels of cleavage complexes with positively supercoiled (compared with negatively supercoiled) DNA, whereas topoisomerase IV generated similar levels with both substrates. Results indicate that gyrase is better suited than topoisomerase IV to safely remove positive supercoils that accumulate ahead of replication forks. They also suggest that the wrapping mechanism of gyrase may have evolved to promote rapid removal of positive supercoils, rather than induction of negative supercoils.
[Mh] Termos MeSH primário: DNA Girase/metabolismo
DNA Topoisomerase IV/metabolismo
DNA Super-Helicoidal/química
DNA Super-Helicoidal/metabolismo
[Mh] Termos MeSH secundário: Bacillus anthracis/enzimologia
DNA Girase/química
DNA Topoisomerase IV/química
Proteínas de Escherichia coli/química
Proteínas de Escherichia coli/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Superhelical); 0 (Escherichia coli Proteins); EC 5.99.1.- (DNA Topoisomerase IV); EC 5.99.1.3 (DNA Gyrase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170922
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx649


  5 / 1021 MEDLINE  
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[PMID]:28842485
[Au] Autor:Kumar R; Nurse P; Bahng S; Lee CM; Marians KJ
[Ad] Endereço:From the Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065.
[Ti] Título:The MukB-topoisomerase IV interaction is required for proper chromosome compaction.
[So] Source:J Biol Chem;292(41):16921-16932, 2017 Oct 13.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The bacterial condensin MukB and the cellular decatenating enzyme topoisomerase IV interact. This interaction stimulates intramolecular reactions catalyzed by topoisomerase IV, supercoiled DNA relaxation, and DNA knotting but not intermolecular reactions such as decatenation of linked DNAs. We have demonstrated previously that MukB condenses DNA by sequestering negative supercoils and stabilizing topologically isolated loops in the DNA. We show here that the MukB-topoisomerase IV interaction stabilizes MukB on DNA, increasing the extent of DNA condensation without increasing the amount of MukB bound to the DNA. This effect does not require the catalytic activity of topoisomerase IV. Cells carrying a mutant allele that encodes a protein that does not interact with topoisomerase IV exhibit severe nucleoid decompaction leading to chromosome segregation defects. These findings suggest that the MukB-topoisomerase IV complex may provide a scaffold for DNA condensation.
[Mh] Termos MeSH primário: Proteínas Cromossômicas não Histona/química
Cromossomos Bacterianos/química
DNA Topoisomerase IV/química
DNA Bacteriano/química
DNA Super-Helicoidal/química
Proteínas de Escherichia coli/química
Escherichia coli/química
Complexos Multiproteicos/química
[Mh] Termos MeSH secundário: Proteínas Cromossômicas não Histona/genética
Proteínas Cromossômicas não Histona/metabolismo
Cromossomos Bacterianos/genética
Cromossomos Bacterianos/metabolismo
DNA Topoisomerase IV/genética
DNA Topoisomerase IV/metabolismo
DNA Bacteriano/genética
DNA Bacteriano/metabolismo
DNA Super-Helicoidal/genética
DNA Super-Helicoidal/metabolismo
Escherichia coli/genética
Escherichia coli/metabolismo
Proteínas de Escherichia coli/genética
Proteínas de Escherichia coli/metabolismo
Complexos Multiproteicos/genética
Complexos Multiproteicos/metabolismo
Mutação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chromosomal Proteins, Non-Histone); 0 (DNA, Bacterial); 0 (DNA, Superhelical); 0 (Escherichia coli Proteins); 0 (MukB protein, E coli); 0 (Multiprotein Complexes); EC 5.99.1.- (DNA Topoisomerase IV)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170827
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.803346


  6 / 1021 MEDLINE  
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[PMID]:28708867
[Au] Autor:Zhu F; Yang Z; Zhang Y; Hu K; Fang W
[Ad] Endereço:National Pathogen Collection Center for Aquatic Animals, Shanghai Ocean University, Shanghai, China.
[Ti] Título:Transcriptome differences between enrofloxacin-resistant and enrofloxacin-susceptible strains of Aeromonas hydrophila.
[So] Source:PLoS One;12(7):e0179549, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Enrofloxacin is the most commonly used antibiotic to control diseases in aquatic animals caused by A. hydrophila. This study conducted de novo transcriptome sequencing and compared the global transcriptomes of enrofloxacin-resistant and enrofloxacin-susceptible strains. We got a total of 4,714 unigenes were assembled. Of these, 4,122 were annotated. A total of 3,280 unigenes were assigned to GO, 3,388 unigenes were classified into Cluster of Orthologous Groups of proteins (COG) using BLAST and BLAST2GO software, and 2,568 were mapped onto pathways using the Kyoto Encyclopedia of Gene and Genomes Pathway database. Furthermore, 218 unigenes were deemed to be DEGs. After enrofloxacin treatment, 135 genes were upregulated and 83 genes were downregulated. The GO terms biological process (126 genes) and metabolic process (136 genes) were the most enriched, and the terms for protein folding, response to stress, and SOS response were also significantly enriched. This study identified enrofloxacin treatment affects multiple biological functions of A. hydrophila. Enrofloxacin resistance in A. hydrophila is closely related to the reduction of intracellular drug accumulation caused by ABC transporters and increased expression of topoisomerase IV.
[Mh] Termos MeSH primário: Aeromonas hydrophila/genética
Farmacorresistência Bacteriana/genética
Fluoroquinolonas/farmacologia
Transcriptoma/efeitos dos fármacos
[Mh] Termos MeSH secundário: Transportadores de Cassetes de Ligação de ATP/genética
Transportadores de Cassetes de Ligação de ATP/metabolismo
Aeromonas hydrophila/efeitos dos fármacos
Aeromonas hydrophila/metabolismo
Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Análise por Conglomerados
DNA Topoisomerase IV/genética
DNA Topoisomerase IV/metabolismo
Bases de Dados Genéticas
Regulação para Baixo/efeitos dos fármacos
Sequenciamento de Nucleotídeos em Larga Escala
RNA Bacteriano/química
RNA Bacteriano/isolamento & purificação
RNA Bacteriano/metabolismo
Análise de Sequência de RNA
Regulação para Cima/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Fluoroquinolones); 0 (RNA, Bacterial); 3DX3XEK1BN (enrofloxacin); EC 5.99.1.- (DNA Topoisomerase IV)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170715
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0179549


  7 / 1021 MEDLINE  
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[PMID]:28671064
[Au] Autor:Tatay-Dualde J; Prats-van der Ham M; de la Fe C; Paterna A; Sánchez A; Corrales JC; Contreras A; Gómez-Martin Á
[Ad] Endereço:Department of Animal Health, Faculty of Veterinary Sciences, Regional Campus of International Excellence 'Campus Mare Nostrum', Universidad de Murcia, Campus de Espinardo s/n, Murcia 30100, Spain.
[Ti] Título:Resistance mechanisms against quinolones in Mycoplasma capricolum subsp. capricolum.
[So] Source:Vet J;223:1-4, 2017 May.
[Is] ISSN:1532-2971
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Quinolones interact with bacterial DNA gyrase and topoisomerase IV, the subunits of which are encoded by gyrA/gyrB and parC/parE, respectively. The aim of this study was to evaluate the relationship between changes in these genes and quinolone susceptibility of Mycoplasma capricolum subsp. capricolum (Mcc). Using in vitro selected resistant mutants and field isolates from goats, predicted amino acid changes in gyrA, gyrB and parC were associated with higher minimum inhibitory concentration values for quinolones. Alterations in parC predicted amino acid sequences were most frequently associated with quinolone resistance in Mcc.
[Mh] Termos MeSH primário: Farmacorresistência Bacteriana/genética
Doenças das Cabras/microbiologia
Mycoplasma capricolum/efeitos dos fármacos
Mycoplasma capricolum/genética
Pleuropneumonia Contagiosa/microbiologia
Quinolonas/farmacologia
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
DNA Girase/química
DNA Girase/genética
DNA Topoisomerase IV/química
DNA Topoisomerase IV/genética
Cabras
Testes de Sensibilidade Microbiana
Mutação
Pleuropneumonia Contagiosa/tratamento farmacológico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Quinolones); EC 5.99.1.- (DNA Topoisomerase IV); EC 5.99.1.3 (DNA Gyrase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170704
[St] Status:MEDLINE


  8 / 1021 MEDLINE  
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[PMID]:28610977
[Au] Autor:Mitton-Fry MJ; Brickner SJ; Hamel JC; Barham R; Brennan L; Casavant JM; Ding X; Finegan S; Hardink J; Hoang T; Huband MD; Maloney M; Marfat A; McCurdy SP; McLeod D; Subramanyam C; Plotkin M; Reilly U; Schafer J; Stone GG; Uccello DP; Wisialowski T; Yoon K; Zaniewski R; Zook C
[Ad] Endereço:Pfizer Worldwide Research and Development, Groton, CT 06340, USA. Electronic address: mitton-fry.1@osu.edu.
[Ti] Título:Novel 3-fluoro-6-methoxyquinoline derivatives as inhibitors of bacterial DNA gyrase and topoisomerase IV.
[So] Source:Bioorg Med Chem Lett;27(15):3353-3358, 2017 08 01.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Novel (non-fluoroquinolone) inhibitors of bacterial type II topoisomerases (NBTIs) are an emerging class of antibacterial agents. We report an optimized series of cyclobutylaryl-substituted NBTIs. Compound 14 demonstrated excellent activity both in vitro (S. aureus MIC =0.125µg/mL) and in vivo (systemic and tissue infections). Enhanced inhibition of Topoisomerase IV correlated with improved activity in S. aureus strains with mutations conferring resistance to NBTIs. Compound 14 also displayed an improved hERG IC of 85.9µM and a favorable profile in the anesthetized guinea pig model.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
DNA Girase/metabolismo
DNA Topoisomerase IV/antagonistas & inibidores
Quinolinas/farmacologia
Inibidores da Topoisomerase II/farmacologia
Inibidores da Topoisomerase/farmacologia
[Mh] Termos MeSH secundário: Animais
Antibacterianos/síntese química
Antibacterianos/química
DNA Topoisomerase IV/metabolismo
Relação Dose-Resposta a Droga
Canais de Potássio Éter-A-Go-Go/metabolismo
Cobaias
Seres Humanos
Testes de Sensibilidade Microbiana
Estrutura Molecular
Quinolinas/síntese química
Quinolinas/química
Staphylococcus aureus/efeitos dos fármacos
Staphylococcus aureus/enzimologia
Streptococcus pyogenes/efeitos dos fármacos
Streptococcus pyogenes/enzimologia
Relação Estrutura-Atividade
Inibidores da Topoisomerase II/síntese química
Inibidores da Topoisomerase II/química
Inibidores da Topoisomerase/síntese química
Inibidores da Topoisomerase/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (3-fluoro-6-methoxyquinoline); 0 (Anti-Bacterial Agents); 0 (Ether-A-Go-Go Potassium Channels); 0 (Quinolines); 0 (Topoisomerase II Inhibitors); 0 (Topoisomerase Inhibitors); EC 5.99.1.- (DNA Topoisomerase IV); EC 5.99.1.3 (DNA Gyrase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171125
[Lr] Data última revisão:
171125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170615
[St] Status:MEDLINE


  9 / 1021 MEDLINE  
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[PMID]:28504927
[Au] Autor:Correia S; Poeta P; Hébraud M; Capelo JL; Igrejas G
[Ad] Endereço:1​Functional Genomics and Proteomics Unit, University of Trás-os-Montes and Alto Douro, Portugal.
[Ti] Título:Mechanisms of quinolone action and resistance: where do we stand?
[So] Source:J Med Microbiol;66(5):551-559, 2017 May.
[Is] ISSN:1473-5644
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Quinolone antibiotics represent one of the most important classes of anti-infective agents and, although still clinically valuable, their use has been compromised by the increasing emergence of resistant strains, which has become a prevalent clinical problem. Quinolones act by inhibiting the activity of DNA gyrase and topoisomerase IV - two essential bacterial enzymes that modulate the chromosomal supercoiling required for critical nucleic acid processes. The acquisition of quinolone resistance is recognized to be multifactorial and complex. The main resistance mechanism consists of one or a combination of target-site gene mutations that alter the drug-binding affinity of target enzymes. However, other mechanisms such as mutations that lead to reduced intracellular drug concentrations, by either decreased uptake or increased efflux, and plasmid-encoded resistance genes producing either target protection proteins, drug-modifying enzymes or multidrug efflux pumps are known to contribute additively to quinolone resistance. The understanding of these different resistance mechanisms has improved significantly in recent years; however, many details remain to be clarified and the contribution of less-studied mechanisms still needs to be better elucidated in order to fully understand this phenotype.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Bactérias/efeitos dos fármacos
Proteínas de Bactérias/genética
Farmacorresistência Bacteriana
Quinolonas/farmacologia
[Mh] Termos MeSH secundário: Antibacterianos/metabolismo
Antibacterianos/uso terapêutico
Bactérias/genética
Bactérias/metabolismo
Proteínas de Bactérias/antagonistas & inibidores
Proteínas de Bactérias/metabolismo
DNA Girase/genética
DNA Girase/metabolismo
DNA Topoisomerase IV/antagonistas & inibidores
DNA Topoisomerase IV/genética
Seres Humanos
Mutação
Plasmídeos
Quinolonas/metabolismo
Quinolonas/uso terapêutico
Inibidores da Topoisomerase/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Bacterial Proteins); 0 (Quinolones); 0 (Topoisomerase Inhibitors); EC 5.99.1.- (DNA Topoisomerase IV); EC 5.99.1.3 (DNA Gyrase)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171110
[Lr] Data última revisão:
171110
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170516
[St] Status:MEDLINE
[do] DOI:10.1099/jmm.0.000475


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Fotocópia
Alves, Luiz Carlos
Texto completo
[PMID]:28425875
[Au] Autor:Scavuzzi AML; Maciel MAV; de Melo HRL; Alves LC; Brayner FA; Lopes ACS
[Ad] Endereço:2​Centro de Pesquisas Aggeu Magalhães (CPqAM-Fiocruz), Recife-PE, Brazil 1​Departamento de Medicina Tropical, Universidade Federal de Pernambuco (UFPE), 50.732-970, Recife-PE, Brazil.
[Ti] Título:Occurrence of qnrB1 and qnrB12 genes, mutation in gyrA and ramR, and expression of efflux pumps in isolates of Klebsiella pneumoniae carriers of blaKPC-2.
[So] Source:J Med Microbiol;66(4):477-484, 2017 Apr.
[Is] ISSN:1473-5644
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:PURPOSE: The occurrence of quinolone-resistance genes (qnrA, qnrB and qnrS), the presence of mutations in gyrA, gyrB and parC, as well as the expression of efflux pumps (acrB and acrF) and mutations in the gene ramR. METHODOLOGY: Were investigated in 30 blaKPC-2-positive isolates of Klebsiella pneumoniae taken from infection and colonization in hospital patients from Recife-PE, Brazil. The detection of the qnr, acrB and acrF genes and analysis of the mutations in ramR and the quinolone-resistance-determining regions of gyrA, gyrB and parC were performed by PCR followed by DNA sequencing. RESULTS: Among the isolates analysed, 73.3 % (n=22) presented the qnrB gene. For the DNA sequencing, six isolates (K3-A2, K12-A2, K25-A2, K27-A2, K19-A2 and K3-C2) were selected and the qnrB1 and qnrB12 variants were detected. This is the first ever report, to the best of our knowledge, of the presence of qnrB12 in K. pneumoniae. This is also the first report, to the best of our knowledge, of the presence of qnrB1 or qnrB12 with blaKPC-2 in K. pneumoniae in Brazil. Mutations were observed in gyrA S83 and in ramR. All isolates presented genes for the acrB and acrF efflux pumps and the reverse transcription PCR performed showed that the pumps were being expressed. CONCLUSION: KPC-2-positive isolates colonizing patients, which also showed qnrB, mutation in gyrA and efflux pumps, may be important reservoirs for disseminating these resistance mechanisms in the hospital environment.
[Mh] Termos MeSH primário: Proteínas de Bactérias/genética
DNA Girase/genética
DNA Topoisomerase IV/genética
Klebsiella pneumoniae/efeitos dos fármacos
Klebsiella pneumoniae/genética
Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética
beta-Lactamases/genética
[Mh] Termos MeSH secundário: Sequência de Bases
Brasil
DNA Bacteriano/genética
Seres Humanos
Klebsiella pneumoniae/isolamento & purificação
Testes de Sensibilidade Microbiana
Reação em Cadeia da Polimerase
Quinolonas/farmacologia
Análise de Sequência de DNA
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (DNA, Bacterial); 0 (Multidrug Resistance-Associated Proteins); 0 (Qnr protein, Klebsiella pneumoniae); 0 (Quinolones); EC 3.5.2.6 (beta-Lactamases); EC 3.5.2.6 (beta-lactamase KPC-2, Klebsiella pneumoniae); EC 5.99.1.- (DNA Topoisomerase IV); EC 5.99.1.3 (DNA Gyrase)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170523
[Lr] Data última revisão:
170523
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170421
[St] Status:MEDLINE
[do] DOI:10.1099/jmm.0.000452



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