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  1 / 1174 MEDLINE  
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[PMID]:28838073
[Au] Autor:Bradshaw CS; Jensen JS; Waites KB
[Ad] Endereço:Central Clinical School, Monash University.
[Ti] Título:New Horizons in Mycoplasma genitalium Treatment.
[So] Source:J Infect Dis;216(suppl_2):S412-S419, 2017 Jul 15.
[Is] ISSN:1537-6613
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mycoplasmagenitalium is an important sexually transmitted pathogen responsible for both male and female genital tract disease. Appreciation of its significance in human disease has been hampered by its slow growth in culture, difficulty in isolating it, and lack of commercial molecular-based tests for rapid detection. Comparatively few in vitro data on antimicrobial susceptibility are available due to the scarcity of clinical isolates and difficulty in performing susceptibility tests to determine minimum inhibitory concentrations for M. genitalium. Antimicrobial agents that inhibit protein synthesis such as macrolides, along with fluoroquinolones that inhibit DNA replication, have been the treatments of choice for M. genitalium infections. Even though international guidelines recommend azithromycin as first-line treatment, rapid spread of macrolide resistance as well as emergence of quinolone resistance has occurred. Increasing rates of treatment failure have resulted in an urgent need for new therapies and renewed interest in other classes such as aminocyclitols, phenicols, and streptogramins as treatment alternatives. Limited data for new investigational antimicrobials such as the ketolide solithromycin suggest that this drug may eventually prove useful in management of some resistant M. genitalium infections, although it is not likely to achieve cure rates >80% in macrolide-resistant strains, in a similar range as recently reported for pristinamycin. However, agents with completely new targets and/or mechanisms that would be less likely to show cross-resistance with currently available drugs may hold the greatest promise. Lefamulin, a pleuromutilin, and new nonquinolone topoisomerase inhibitors are attractive possibilities that require further investigation.
[Mh] Termos MeSH primário: Antibacterianos/uso terapêutico
Descoberta de Drogas/classificação
Infecções por Mycoplasma/diagnóstico
Infecções por Mycoplasma/tratamento farmacológico
[Mh] Termos MeSH secundário: Azitromicina/uso terapêutico
Farmacorresistência Bacteriana
Feminino
Fluoroquinolonas/uso terapêutico
Seres Humanos
Masculino
Testes de Sensibilidade Microbiana
Mycoplasma genitalium
Quinolinas/uso terapêutico
Espectinomicina/uso terapêutico
Estreptograminas/uso terapêutico
Tetraciclinas/uso terapêutico
Tianfenicol/uso terapêutico
Falha de Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Fluoroquinolones); 0 (Quinolines); 0 (Streptogramins); 0 (Tetracyclines); 83905-01-5 (Azithromycin); 93AKI1U6QF (Spectinomycin); E66400VT9R (quinoline); FLQ7571NPM (Thiamphenicol)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170826
[St] Status:MEDLINE
[do] DOI:10.1093/infdis/jix132


  2 / 1174 MEDLINE  
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[PMID]:28545411
[Au] Autor:Jiang FX; Lan Q; Le WJ; Su XH
[Ad] Endereço:Department of Dermatology, Anhui Provincial Hospital, Hefei, 230001, China.
[Ti] Título:Antimicrobial susceptibility of Neisseria gonorrhoeae isolates from Hefei (2014-2015): genetic characteristics of antimicrobial resistance.
[So] Source:BMC Infect Dis;17(1):366, 2017 May 25.
[Is] ISSN:1471-2334
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Antimicrobial resistance (AMR) and genetic determinants of resistance of N. gonorrhoeae isolates from Hefei, China, were characterized adding a breadth of information to the molecular epidemiology of gonococcal resistance in China. METHODS: 126 N. gonorrhoeae isolates from a hospital clinic in Hefei, were collected between January, 2014, and November, 2015. The minimum inhibitory concentration (MIC) of N. gonorrhoeae isolates for seven antimicrobials were determined by the agar dilution method. Isolates were tested for mutations in penA and mtrR genes and 23S rRNA, and also genotyped using N. gonorrhoeae multi-antigen sequence typing (NG-MAST). RESULTS: All N. gonorrhoeae isolates were resistant to ciprofloxacin; 81.7% (103/126) to tetracycline and 73.8% (93/126) to penicillin. 39.7% (50/126) of isolates were penicillinase producing N. gonorrhoeae (PPNG), 31.7% (40/126) were tetracycline resistant N. gonorrhoeae (TRNG) and 28.6% (36/126) were resistant to azithromycin. While not fully resistant to extended spectrum cephalosporins (ESCs), a total of 14 isolates (11.1%) displayed decreased susceptibility to ceftriaxone (MIC ≥ 0.125 mg/L, n = 10), cefixime (MIC ≥ 0. 25 mg/L, n = 1) or to both ESCs (n = 3). penA mosaic alleles XXXV were found in all isolates that harbored decreased susceptibility to cefixime, except for one. Four mutations were found in mtrR genes and mutations A2143G and C2599T were identified in 23S rRNA. No isolates were resistant to spectinomycin. Gonococcal isolates were distributed into diverse NG-MAST sequence types (STs); 86 separate STs were identified. CONCLUSIONS: N. gonorrhoeae isolates from Hefei during 2014-2015, displayed high levels of resistance to antimicrobials that had been recommended previously for treatment of gonorrhea, e.g., penicillin, tetracycline and ciprofloxacin. The prevalence of resistance to azithromycin was also high (28.6%). No isolates were found to be fully resistant to spectinomycin, ceftriaxone or cefixime; however, 11.1% isolates, overall, had decreased susceptibility to ESCs.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Farmacorresistência Bacteriana/genética
Gonorreia/microbiologia
Neisseria gonorrhoeae/efeitos dos fármacos
Neisseria gonorrhoeae/genética
[Mh] Termos MeSH secundário: Azitromicina/farmacologia
Proteínas de Bactérias/genética
Cefalosporinas/farmacologia
China/epidemiologia
Ciprofloxacino/farmacologia
Farmacorresistência Bacteriana/efeitos dos fármacos
Genótipo
Gonorreia/epidemiologia
Seres Humanos
Testes de Sensibilidade Microbiana
Epidemiologia Molecular
Mutação
Neisseria gonorrhoeae/isolamento & purificação
Penicilinas/farmacologia
Proteínas Repressoras/genética
Espectinomicina/farmacologia
Tetraciclina/farmacologia
beta-Lactamases/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Bacterial Proteins); 0 (Cephalosporins); 0 (Penicillins); 0 (Repressor Proteins); 155359-99-2 (mtrR protein, Neisseria gonorrhoeae); 5E8K9I0O4U (Ciprofloxacin); 83905-01-5 (Azithromycin); 93AKI1U6QF (Spectinomycin); EC 3.5.2.6 (beta-Lactamases); F8VB5M810T (Tetracycline)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170911
[Lr] Data última revisão:
170911
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170527
[St] Status:MEDLINE
[do] DOI:10.1186/s12879-017-2472-z


  3 / 1174 MEDLINE  
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[PMID]:28158667
[Au] Autor:Jeamton W; Dulsawat S; Tanticharoen M; Vonshak A; Cheevadhanarak S
[Ad] Endereço:Pilot Plant Development and Training Institute, King Mongkut's University of Technology Thonburi (Bang Khun Thian), Bangkok, Thailand.
[Ti] Título:Overcoming Intrinsic Restriction Enzyme Barriers Enhances Transformation Efficiency in Arthrospira platensis C1.
[So] Source:Plant Cell Physiol;58(4):822-830, 2017 04 01.
[Is] ISSN:1471-9053
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:The development of a reliable genetic transformation system for Arthrospira platensis has been a long-term goal, mainly for those trying either to improve its performance in large-scale cultivation systems or to enhance its value as food and feed additives. However, so far, most of the attempts to develop such a transformation system have had limited success. In this study, an efficient and stable transformation system for A. platensis C1 was successfully developed. Based on electroporation and transposon techniques, exogenous DNA could be transferred to and stably maintained in the A. platensis C1 genome. Most strains of Arthrospira possess strong restriction barriers, hampering the development of a gene transfer system for this group of cyanobacteria. By using a type I restriction inhibitor and liposomes to protect the DNA from nuclease digestion, the transformation efficiency was significantly improved. The transformants were able to grow on a selective medium for more than eight passages, and the transformed DNA could be detected from the stable transformants. We propose that the intrinsic endonuclease enzymes, particularly the type I restriction enzyme, in A. platensis C1 play an important role in the transformation efficiency of this industrial important cyanobacterium.
[Mh] Termos MeSH primário: Enzimas/metabolismo
Spirulina/enzimologia
Spirulina/genética
Transformação Genética
[Mh] Termos MeSH secundário: Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Meios de Cultura/química
Meios de Cultura/farmacologia
Elementos de DNA Transponíveis
Farmacorresistência Bacteriana/genética
Enzimas/genética
Genoma Bacteriano
Plasmídeos
Reação em Cadeia da Polimerase
Regiões Promotoras Genéticas
Reprodutibilidade dos Testes
Espectinomicina/farmacologia
Spirulina/efeitos dos fármacos
Transposases/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Culture Media); 0 (DNA Transposable Elements); 0 (Enzymes); 0 (Tn5 transposase); 93AKI1U6QF (Spectinomycin); EC 2.7.7.- (Transposases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170204
[St] Status:MEDLINE
[do] DOI:10.1093/pcp/pcx016


  4 / 1174 MEDLINE  
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[PMID]:28152054
[Au] Autor:Zhang G; Leclercq SO; Tian J; Wang C; Yahara K; Ai G; Liu S; Feng J
[Ad] Endereço:State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
[Ti] Título:A new subclass of intrinsic aminoglycoside nucleotidyltransferases, ANT(3")-II, is horizontally transferred among Acinetobacter spp. by homologous recombination.
[So] Source:PLoS Genet;13(2):e1006602, 2017 Feb.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The emergence and spread of antibiotic resistance among Acinetobacter spp. have been investigated extensively. Most studies focused on the multiple antibiotic resistance genes located on plasmids or genomic resistance islands. On the other hand, the mechanisms controlling intrinsic resistance are still not well understood. In this study, we identified the novel subclass of aminoglycoside nucleotidyltransferase ANT(3")-II in Acinetobacter spp., which comprised numerous variants distributed among three main clades. All members of this subclass can inactivate streptomycin and spectinomycin. The three ant(3")-II genes, encoding for the three ANT(3")-II clades, are widely distributed in the genus Acinetobacter and always located in the same conserved genomic region. According to their prevalence, these genes are intrinsic in Acinetobacter baumannii, Acinetobacter pittii, and Acinetobacter gyllenbergii. We also demonstrated that the ant(3")-II genes are located in a homologous recombination hotspot and were recurrently transferred among Acinetobacter species. In conclusion, our findings demonstrated a novel mechanism of natural resistance in Acinetobacter spp., identified a novel subclass of aminoglycoside nucleotidyltransferase and provided new insight into the evolutionary history of intrinsic resistance genes.
[Mh] Termos MeSH primário: Acinetobacter/genética
Proteínas de Bactérias/genética
Transferência Genética Horizontal
Recombinação Homóloga
Nucleotidiltransferases/genética
[Mh] Termos MeSH secundário: Acinetobacter/classificação
Acinetobacter/enzimologia
Infecções por Acinetobacter/microbiologia
Acinetobacter baumannii/enzimologia
Acinetobacter baumannii/genética
Proteínas de Bactérias/metabolismo
Resistência Microbiana a Medicamentos/efeitos dos fármacos
Resistência Microbiana a Medicamentos/genética
Eletroforese em Gel de Poliacrilamida
Interações Hospedeiro-Patógeno
Seres Humanos
Testes de Sensibilidade Microbiana
Nucleotidiltransferases/metabolismo
Filogenia
Especificidade da Espécie
Espectinomicina/metabolismo
Espectinomicina/farmacologia
Estreptomicina/metabolismo
Estreptomicina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 93AKI1U6QF (Spectinomycin); EC 2.7.7.- (Nucleotidyltransferases); EC 2.7.7.47 (streptomycin 3''-adenylyltransferase); Y45QSO73OB (Streptomycin)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170607
[Lr] Data última revisão:
170607
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170203
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1006602


  5 / 1174 MEDLINE  
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[PMID]:28039273
[Au] Autor:Moran RA; Anantham S; Holt KE; Hall RM
[Ad] Endereço:School of Life and Environmental Sciences, The University of Sydney, NSW 2006, Australia.
[Ti] Título:Prediction of antibiotic resistance from antibiotic resistance genes detected in antibiotic-resistant commensal Escherichia coli using PCR or WGS.
[So] Source:J Antimicrob Chemother;72(3):700-704, 2017 Mar 01.
[Is] ISSN:1460-2091
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Objectives: To assess the effectiveness of bioinformatic detection of resistance genes in whole-genome sequences in correctly predicting resistance phenotypes. Methods: Genomes of a collection of well-characterized commensal Escherichia coli were sequenced using Illumina HiSeq technology and assembled with SPAdes. Antibiotic resistance genes identified by PCR, SRST2 analysis of reads and ResFinder analysis of SPAdes assemblies were compared with known resistance phenotypes. Results: Generally, the antibiotic resistance genes detected using bioinformatic methods were concordant, but only ARG-ANNOT included sat2 . However, the presence or absence of genes was not always predictive of the phenotype. In one strain, trimethoprim resistance was due to a known mutation in the chromosomal folA gene. In cases where the copy number was low, the aadA5 gene downstream of dfrA17 did not confer streptomycin or spectinomycin resistance. Resistance genes were found in the genomes that were not detected previously by PCRs targeting a limited gene set and gene cassettes in class 1 or class 2 integrons. In one isolate, the aadA1 gene cassette in the estX - aadA1 cassettes pair was outside an integron context and was not expressed. The qnrS1 gene, conferring reduced susceptibility to fluoroquinolones, and the bla CMY-2 gene, encoding an ESBL, were each detected in a single isolate and mphA (macrolide resistance) was present in six isolates surrounded by IS 26 and IS 6100 . Conclusions: WGS analysis detected more genes than PCR. Some were not expressed, causing inconsistencies with the experimentally determined phenotype. An unpredicted chromosomal folA mutation causing trimethoprim resistance was found.
[Mh] Termos MeSH primário: DNA Bacteriano/genética
Farmacorresistência Bacteriana
Escherichia coli/efeitos dos fármacos
Escherichia coli/genética
Genoma Bacteriano
Simbiose
[Mh] Termos MeSH secundário: Antibacterianos/farmacologia
Biologia Computacional/métodos
Farmacorresistência Bacteriana/genética
Escherichia coli/isolamento & purificação
Infecções por Escherichia coli/microbiologia
Genes Bacterianos
Sequenciamento de Nucleotídeos em Larga Escala/métodos
Testes de Sensibilidade Microbiana
Fenótipo
Reação em Cadeia da Polimerase/métodos
Espectinomicina/farmacologia
Estreptomicina/farmacologia
Resistência a Trimetoprima/genética
beta-Lactamases/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (DNA, Bacterial); 93AKI1U6QF (Spectinomycin); EC 3.5.2.- (beta-lactamase CMY-2); EC 3.5.2.6 (beta-Lactamases); Y45QSO73OB (Streptomycin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170101
[St] Status:MEDLINE
[do] DOI:10.1093/jac/dkw511


  6 / 1174 MEDLINE  
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[PMID]:27999043
[Au] Autor:Lahra MM; Trembizki E; Buckley C; Donovan B; Chen M; Guy R; Kundu RL; Regan DG; Whiley DM; GRAND Study Investigators
[Ad] Endereço:WHO Collaborating Centre for STD, Microbiology Department, South Eastern Area Laboratory Services, Prince of Wales Hospital, Randwick, New South Wales 2031, Australia.
[Ti] Título:Changes in the rates of Neisseria gonorrhoeae antimicrobial resistance are primarily driven by dynamic fluctuations in common gonococcal genotypes.
[So] Source:J Antimicrob Chemother;72(3):705-711, 2017 Mar 01.
[Is] ISSN:1460-2091
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Objectives: To examine how gonococcal genotypes and associated changes over time influence rates of Neisseria gonorrhoeae antimicrobial resistance. Methods: All available N. gonorrhoeae isolates collected in New South Wales, Australia in the first half of both 2012 and 2014 were genotyped using the Agena MassARRAY iPLEX platform. Genotypic data were compared with phenotypic antimicrobial resistance profiles over time. We focused on penicillin and ciprofloxacin as significant increases in resistance to both antibiotics were observed over this time period. Results: Genotyping data were obtained for 760 and 782 isolates in 2012 and 2014, respectively. A total of 162 distinct genotypes were identified in the study, including 36 (22.2%) genotypes present in both years ( persisting genotypes), 54 (33.3%) observed in 2012 only and 72 (44.4%) observed in 2014 only (s ingle-year genotypes). Overall, persisting genotypes comprised 15 of the 20 most common genotypes, 8 of which showed a significant change in proportion from 2012 to 2014. Persisting genotypes also comprised the majority (>70%) of ciprofloxacin- and penicillin-resistant isolates in both years. Significant fluctuations in the most common persisting genotypes accounted for the majority of observed increases in both ciprofloxacin and penicillin resistance. Single-year genotypes contributed to ∼20% of ciprofloxacin and penicillin resistance in each year. Conclusions: The results show that the gonococcal genotypes persisting in the study population fluctuated significantly within a 3 year period, with numerous other genotypes appearing or disappearing. It is the net effect of these changes that determines N. gonorrhoeae antimicrobial resistance levels within the population.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Farmacorresistência Bacteriana Múltipla/genética
Gonorreia/epidemiologia
Neisseria gonorrhoeae/efeitos dos fármacos
Neisseria gonorrhoeae/genética
[Mh] Termos MeSH secundário: Austrália/epidemiologia
Ceftriaxona/farmacologia
Ciprofloxacino/farmacologia
DNA Bacteriano/genética
Genótipo
Gonorreia/microbiologia
Testes de Sensibilidade Microbiana
Resistência às Penicilinas/genética
Penicilinas/farmacologia
Espectinomicina/farmacologia
Resistência a Tetraciclina/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (DNA, Bacterial); 0 (Penicillins); 5E8K9I0O4U (Ciprofloxacin); 75J73V1629 (Ceftriaxone); 93AKI1U6QF (Spectinomycin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161222
[St] Status:MEDLINE
[do] DOI:10.1093/jac/dkw452


  7 / 1174 MEDLINE  
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[PMID]:27999020
[Au] Autor:Robertson GT; Scherman MS; Bruhn DF; Liu J; Hastings C; McNeil MR; Butler MM; Bowlin TL; Lee RB; Lee RE; Lenaerts AJ
[Ad] Endereço:Mycobacterial Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA.
[Ti] Título:Spectinamides are effective partner agents for the treatment of tuberculosis in multiple mouse infection models.
[So] Source:J Antimicrob Chemother;72(3):770-777, 2017 Mar 01.
[Is] ISSN:1460-2091
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Objectives: New drug regimens employing combinations of existing and experimental antimicrobial agents are needed to shorten treatment of tuberculosis (TB) in humans. The spectinamides are narrow-spectrum semisynthetic analogues of spectinomycin, modified to avoid intrinsic efflux by Mycobacterium tuberculosis . Spectinamides, including lead 1599, have been previously shown to exhibit a promising therapeutic profile in mice as single agents. Here we explore the in vivo activity of lead spectinamides when combined with other agents. Methods: The efficacy of 1599 or 1810 was tested in combination in three increasingly advanced TB mouse models. Mice were infected by aerosol and allowed to establish acute or chronic infection, followed by treatment (≤4 weeks) with the spectinamides alone or in two- and three-drug combination regimens with existing and novel therapeutic agents. Bacteria were enumerated from lungs by plating for cfu. Results: Herein we show the following: (i) 1599 exhibits additive or synergistic activity with most of the first-line agents; (ii) 1599 in combination with rifampicin and pyrazinamide or with bedaquiline and pyrazinamide promotes significantly improved efficacy in the high-dose aerosol model; (iii) 1599 enhances efficacy of rifampicin or pyrazinamide in chronically infected BALB/c mice; and (iv) 1599 is synergistic when administered in combination with rifampicin and pyrazinamide in the C3HeB/FeJ mouse model showing caseous necrotic pulmonary lesions. Conclusions: Spectinamides were effective partner agents for multiple anti-TB agents including bedaquiline, rifampicin and pyrazinamide. None of these in vivo synergistic interactions was predicted from in vitro MIC chequerboard assays. These data support further development of the spectinamides as combination partners with existing and experimental anti-TB agents.
[Mh] Termos MeSH primário: Antituberculosos/uso terapêutico
Espectinomicina/química
Espectinomicina/uso terapêutico
Tuberculose/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Modelos Animais de Doenças
Sinergismo Farmacológico
Quimioterapia Combinada
Pulmão/efeitos dos fármacos
Pulmão/microbiologia
Camundongos
Camundongos Endogâmicos BALB C
Mycobacterium tuberculosis/efeitos dos fármacos
Pirazinamida/uso terapêutico
Quinolinas/uso terapêutico
Rifampina/uso terapêutico
Tuberculose/microbiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antitubercular Agents); 0 (Quinolines); 2KNI5N06TI (Pyrazinamide); 93AKI1U6QF (Spectinomycin); VJT6J7R4TR (Rifampin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171011
[Lr] Data última revisão:
171011
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161222
[St] Status:MEDLINE
[do] DOI:10.1093/jac/dkw467


  8 / 1174 MEDLINE  
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[PMID]:27855073
[Au] Autor:Kamath D; Gregory ST; O'Connor M
[Ad] Endereço:School of Biological Sciences, University of Missouri-Kansas City, Kansas City, Missouri, USA.
[Ti] Título:The Loop 2 Region of Ribosomal Protein uS5 Influences Spectinomycin Sensitivity, Translational Fidelity, and Ribosome Biogenesis.
[So] Source:Antimicrob Agents Chemother;61(2), 2017 Feb.
[Is] ISSN:1098-6596
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ribosomal protein uS5 is an essential component of the small ribosomal subunit that is involved in subunit assembly, maintenance of translational fidelity, and the ribosome's response to the antibiotic spectinomycin. While many of the characterized uS5 mutations that affect decoding map to its interface with uS4, more recent work has shown that residues distant from the uS4-uS5 interface can also affect the decoding process. We targeted one such interface-remote area, the loop 2 region (residues 20 to 31), for mutagenesis in Escherichia. coli and generated 21 unique mutants. A majority of the loop 2 alterations confer resistance to spectinomycin and affect the fidelity of translation. However, only a minority show altered rRNA processing or ribosome biogenesis defects.
[Mh] Termos MeSH primário: Escherichia coli/efeitos dos fármacos
Proteínas Ribossômicas/química
Proteínas Ribossômicas/metabolismo
Ribossomos/efeitos dos fármacos
Espectinomicina/farmacologia
[Mh] Termos MeSH secundário: Farmacorresistência Bacteriana/efeitos dos fármacos
Farmacorresistência Bacteriana/genética
Escherichia coli/genética
Proteínas de Escherichia coli/química
Proteínas de Escherichia coli/genética
Proteínas de Escherichia coli/metabolismo
Mutação
Biossíntese de Proteínas
RNA Ribossômico/genética
RNA Ribossômico/metabolismo
Proteínas Ribossômicas/genética
Ribossomos/genética
Ribossomos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Escherichia coli Proteins); 0 (RNA, Ribosomal); 0 (Ribosomal Proteins); 0 (ribosomal protein S5); 93AKI1U6QF (Spectinomycin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170918
[Lr] Data última revisão:
170918
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161118
[St] Status:MEDLINE


  9 / 1174 MEDLINE  
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[PMID]:27733515
[Au] Autor:Köhler D; Helm S; Agne B; Baginsky S
[Ad] Endereço:Institute of Biochemistry and Biotechnology, Martin-Luther-University Halle-Wittenberg, Biozentrum, 06120 Halle (Saale), Germany.
[Ti] Título:Importance of Translocon Subunit Tic56 for rRNA Processing and Chloroplast Ribosome Assembly.
[So] Source:Plant Physiol;172(4):2429-2444, 2016 Dec.
[Is] ISSN:1532-2548
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Toc159-containing complexes at the outer chloroplast envelope membrane form stable supercomplexes with a 1-MD translocon at the inner chloroplast envelope membrane of which Tic56 is one essential subunit. While the single mutants tic56-1 and ppi2 (toc159) have an albino phenotype and are able to grow heterotrophically, we find the double mutant to be embryo lethal. Comprehensive quantitative proteome profiling with both single mutants in combination with GeneChip analyses identified a posttranscriptional defect in the accumulation of plastid ribosomal proteins and diminished expression of plastid encoded proteins. In the tic56-1 mutant, the assembly of functional ribosomes is furthermore hampered by a processing defect of the plastid 23S rRNA. Spectinomycin-treatment of wild-type plants phenocopies the molecular phenotype of plastid proteome accumulation in tic56-1 and to a smaller degree also ppi2 plastids, suggesting that a defect in plastid translation is largely responsible for the phenotype of both import mutants. Import experiments with the tic56-3 mutant revealed no significant defect in the import of small ribosomal protein 16 in the absence of full-length Tic56, suggesting that the defect in ribosome assembly in tic56-1 may be independent of a function of Tic56 in protein import. Our data establish a previously unknown link between plastid protein import, the processing of plastid rRNAs, and the assembly of plastid ribosomes and provide further knowledge on the function of the translocon components and the molecular basis for their albino phenotype.
[Mh] Termos MeSH primário: Proteínas de Arabidopsis/metabolismo
Arabidopsis/genética
Cloroplastos/metabolismo
Proteínas de Membrana Transportadoras/metabolismo
Subunidades Proteicas/metabolismo
Processamento Pós-Transcricional do RNA/genética
RNA Ribossômico/genética
Ribossomos/metabolismo
[Mh] Termos MeSH secundário: Arabidopsis/efeitos dos fármacos
Proteínas de Arabidopsis/genética
Proteínas de Cloroplastos/metabolismo
Cloroplastos/efeitos dos fármacos
Proteínas de Membrana Transportadoras/genética
Mutação/genética
Análise de Sequência com Séries de Oligonucleotídeos
Fenótipo
Biossíntese de Proteínas/efeitos dos fármacos
Proteoma/metabolismo
Proteômica
Processamento Pós-Transcricional do RNA/efeitos dos fármacos
RNA Ribossômico/metabolismo
Proteínas Ribossômicas/metabolismo
Ribossomos/efeitos dos fármacos
Sementes/efeitos dos fármacos
Sementes/metabolismo
Espectinomicina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Arabidopsis Proteins); 0 (Chloroplast Proteins); 0 (Membrane Transport Proteins); 0 (Protein Subunits); 0 (Proteome); 0 (RNA, Ribosomal); 0 (Ribosomal Proteins); 0 (Tic56 protein, Arabidopsis); 93AKI1U6QF (Spectinomycin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161014
[St] Status:MEDLINE


  10 / 1174 MEDLINE  
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[PMID]:27707889
[Au] Autor:Parker N; Wang Y; Meinke D
[Ad] Endereço:Department of Plant Biology, Ecology, and Evolution, Oklahoma State University, Stillwater, Oklahoma 74078.
[Ti] Título:Analysis of Arabidopsis Accessions Hypersensitive to a Loss of Chloroplast Translation.
[So] Source:Plant Physiol;172(3):1862-1875, 2016 Nov.
[Is] ISSN:1532-2548
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Natural accessions of Arabidopsis (Arabidopsis thaliana) differ in their ability to tolerate a loss of chloroplast translation. These differences can be attributed in part to variation in a duplicated nuclear gene (ACC2) that targets homomeric acetyl-coenzyme A carboxylase (ACCase) to plastids. This functional redundancy allows limited fatty acid biosynthesis to occur in the absence of heteromeric ACCase, which is encoded in part by the plastid genome. In the presence of functional ACC2, tolerant alleles of several nuclear genes, not yet identified, enhance the growth of seedlings and embryos disrupted in chloroplast translation. ACC2 knockout mutants, by contrast, are hypersensitive. Here we describe an expanded search for hypersensitive accessions of Arabidopsis, evaluate whether all of these accessions are defective in ACC2, and characterize genotype-to-phenotype relationships for homomeric ACCase variants identified among 855 accessions with sequenced genomes. Null alleles with ACC2 nonsense mutations, frameshift mutations, small deletions, genomic rearrangements, and defects in RNA splicing are included among the most sensitive accessions examined. By contrast, most missense mutations affecting highly conserved residues failed to eliminate ACC2 function. Several accessions were identified where sensitivity could not be attributed to a defect in either ACC2 or Tic20-IV, the chloroplast membrane channel required for ACC2 uptake. Overall, these results underscore the central role of ACC2 in mediating Arabidopsis response to a loss of chloroplast translation, highlight future applications of this system to analyzing chloroplast protein import, and provide valuable insights into the mutational landscape of an important metabolic enzyme that is highly conserved throughout eukaryotes.
[Mh] Termos MeSH primário: Arabidopsis/metabolismo
Cloroplastos/metabolismo
Ecótipo
Biossíntese de Proteínas
[Mh] Termos MeSH secundário: Substituição de Aminoácidos/genética
Arabidopsis/efeitos dos fármacos
Arabidopsis/genética
Proteínas de Arabidopsis/genética
Sequência de Bases
Sequência Conservada
Técnicas de Inativação de Genes
Testes Genéticos
Germinação/efeitos dos fármacos
Germinação/genética
Mutação de Sentido Incorreto/genética
Genética Reversa
Plântulas/efeitos dos fármacos
Plântulas/genética
Espectinomicina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Arabidopsis Proteins); 93AKI1U6QF (Spectinomycin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161106
[St] Status:MEDLINE



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