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[PMID]:28755474
[Au] Autor:McKay R; Hauk P; Wu HC; Pottash AE; Shang W; Terrell J; Payne GF; Bentley WE
[Ad] Endereço:Fischell Department of Bioengineering, University of Maryland, College Park, Maryland.
[Ti] Título:Controlling localization of Escherichia coli populations using a two-part synthetic motility circuit: An accelerator and brake.
[So] Source:Biotechnol Bioeng;114(12):2883-2895, 2017 Dec.
[Is] ISSN:1097-0290
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Probiotics, whether taken as capsules or consumed in foods, have been regarded as safe for human use by regulatory agencies. Being living cells, they serve as "tunable" factories for the synthesis of a vast array of beneficial molecules. The idea of reprogramming probiotics to act as controllable factories, producing potential therapeutic molecules under user-specified conditions, represents a new and powerful concept in drug synthesis and delivery. Probiotics that serve as drug delivery vehicles pose several challenges, one being targeting (as seen with nanoparticle approaches). Here, we employ synthetic biology to control swimming directionality in a process referred to as "pseudotaxis." Escherichia coli, absent the motility regulator cheZ, swim sporadically, missing the traditional "run" in the run:tumble swimming paradigm. Upon introduction of cheZ in trans and its signal-generated upregulation, engineered bacteria can be "programmed" to swim toward the source of the chemical cue. Here, engineered cells that encounter sufficient levels of the small signal molecule pyocyanin, produce an engineered CheZ and swim with programmed directionality. By incorporating a degradation tag at the C-terminus of CheZ, the cells stop running when they exit spaces containing pyocyanin. That is, the engineered CheZ modified with a C-terminal extension derived from the putative DNA-binding transcriptional regulator YbaQ (RREERAAKKVA) is consumed by the ClpXP protease machine at a rate sufficient to "brake" the cells when pyocyanin levels are too low. Through this process, we demonstrate that over time, these engineered E. coli accumulate in pyocyanin-rich locales. We suggest that such approaches may find utility in engineering probiotics so that their beneficial functions can be focused in areas of principal benefit.
[Mh] Termos MeSH primário: Quimiotaxia/fisiologia
Proteínas de Escherichia coli/genética
Escherichia coli/fisiologia
Redes Reguladoras de Genes/genética
Melhoramento Genético/métodos
Proteínas Quimiotáticas Aceptoras de Metil/genética
Transativadores/genética
[Mh] Termos MeSH secundário: Quimiotaxia/efeitos dos fármacos
Escherichia coli/efeitos dos fármacos
Piocianina/administração & dosagem
Biologia Sintética/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Escherichia coli Proteins); 0 (Methyl-Accepting Chemotaxis Proteins); 0 (Trans-Activators); 0 (cheZ protein, E coli); 137804-82-1 (SoxS protein, E coli); 9OQM399341 (Pyocyanine)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170730
[St] Status:MEDLINE
[do] DOI:10.1002/bit.26391


  2 / 428 MEDLINE  
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[PMID]:28738346
[Au] Autor:Li Y; Huang J; Li L; Liu L
[Ad] Endereço:State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
[Ti] Título:Synergistic Activity of Berberine with Azithromycin against Pseudomonas Aeruginosa Isolated from Patients with Cystic Fibrosis of Lung In Vitro and In Vivo.
[So] Source:Cell Physiol Biochem;42(4):1657-1669, 2017.
[Is] ISSN:1421-9778
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIMS: Pseudomonas aeruginosa (PA) is one of the major opportunistic pathogens which can cause chronic lung infection of cystic fibrosis (CF). The formation of PA biofilm promotes CF development and restricts the antimicrobial efficacies of current antibiotics. METHODS: The antimicrobial effects of azithromycin (AZM) and berberine (BER) alone and in combination were evaluated using microdilution method, checkerboard assay, time-kill test, qRT-PCR analysis and absorption method. The treatments of AZM and/or BER were further evaluated in an animal lung infection model via observing survival rate, bacterial burden and histopathology of lung, the levels of pro-/anti-inflammatory cytokines. RESULTS: AZM-BER were demonstrated to be synergistic against ten clinical PA isolates as well as the standard reference PA ATCC27853, in which PA03 was the most susceptible isolate to AZM-BER with FICI of 0.13 and chosen for subsequent experiments. The synergism of AZM-BER was further confirmed against PA03 in time-kill test and scanning electron microscope (SEM) at their concentrations showing synergism. In PA03, we found that AZM-BER could significantly attenuate productions of a series of virulence factors including alginate, LasA protease, LasB protease, pyoverdin, pyocyanin, chitinase as well as extracellular DNA, and remarkably inhibit the levels of quorum sensing (QS) molecules and the expressions of lasI, lasR, rhlI, rhlR at 1/2×MIC, 1×MIC and 2×MIC. In the infection model, the mice survival were increased markedly, the inflammations of infected lungs were improved greatly along with reduced IL-6, IL-8 and ascended IL-10 at 0.8 mg/kg of AZM combined with 3.2 mg/kg of BER. CONCLUSION: BER might be a promising synergist to enhance the antimicrobial activity of AZM in vitro and in vivo.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Azitromicina/farmacologia
Berberina/farmacologia
Biofilmes/efeitos dos fármacos
Infecções por Pseudomonas/tratamento farmacológico
Pseudomonas aeruginosa/efeitos dos fármacos
[Mh] Termos MeSH secundário: Alginatos
Animais
Proteínas de Bactérias/antagonistas & inibidores
Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Biofilmes/crescimento & desenvolvimento
Quitinases/antagonistas & inibidores
Quitinases/genética
Quitinases/metabolismo
Ciclofosfamida
Fibrose Cística/microbiologia
DNA Bacteriano/antagonistas & inibidores
DNA Bacteriano/biossíntese
Combinação de Medicamentos
Sinergismo Farmacológico
Ácido Glucurônico/antagonistas & inibidores
Ácido Glucurônico/biossíntese
Ácidos Hexurônicos/antagonistas & inibidores
Seres Humanos
Pulmão/efeitos dos fármacos
Pulmão/metabolismo
Pulmão/microbiologia
Metaloendopeptidases/antagonistas & inibidores
Metaloendopeptidases/genética
Metaloendopeptidases/metabolismo
Metaloproteases/antagonistas & inibidores
Metaloproteases/genética
Metaloproteases/metabolismo
Camundongos
Camundongos Endogâmicos BALB C
Testes de Sensibilidade Microbiana
Neutropenia/induzido quimicamente
Neutropenia/tratamento farmacológico
Neutropenia/genética
Neutropenia/patologia
Oligopeptídeos/antagonistas & inibidores
Oligopeptídeos/biossíntese
Infecções por Pseudomonas/induzido quimicamente
Infecções por Pseudomonas/genética
Infecções por Pseudomonas/patologia
Pseudomonas aeruginosa/crescimento & desenvolvimento
Pseudomonas aeruginosa/patogenicidade
Piocianina/antagonistas & inibidores
Piocianina/biossíntese
Fatores de Virulência/antagonistas & inibidores
Fatores de Virulência/genética
Fatores de Virulência/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Alginates); 0 (Anti-Bacterial Agents); 0 (Bacterial Proteins); 0 (DNA, Bacterial); 0 (Drug Combinations); 0 (Hexuronic Acids); 0 (Oligopeptides); 0 (Virulence Factors); 0I8Y3P32UF (Berberine); 8062-00-8 (pyoverdin); 83905-01-5 (Azithromycin); 8A5D83Q4RW (Glucuronic Acid); 8C3Z4148WZ (alginic acid); 8N3DW7272P (Cyclophosphamide); 9OQM399341 (Pyocyanine); EC 3.2.1.14 (Chitinases); EC 3.4.- (LasA protein, Pseudomonas aeruginosa); EC 3.4.- (Metalloproteases); EC 3.4.24.- (Metalloendopeptidases); EC 3.4.24.26 (pseudolysin, Pseudomonas aeruginosa)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170725
[St] Status:MEDLINE
[do] DOI:10.1159/000479411


  3 / 428 MEDLINE  
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[PMID]:28647320
[Au] Autor:Yong XY; Yan ZY; Shen HB; Zhou J; Wu XY; Zhang LJ; Zheng T; Jiang M; Wei P; Jia HH; Yong YC
[Ad] Endereço:College of Biotechnology and Pharmaceutical Engineering, Bioenergy Research Institute, Nanjing TECH University, Nanjing 211816, China.
[Ti] Título:An integrated aerobic-anaerobic strategy for performance enhancement of Pseudomonas aeruginosa-inoculated microbial fuel cell.
[So] Source:Bioresour Technol;241:1191-1196, 2017 Oct.
[Is] ISSN:1873-2976
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Microbial fuel cell (MFC) is a promising device for energy generation and organic waste treatment simultaneously by electrochemically active bacteria (EAB). In this study, an integrated aerobic-anaerobic strategy was developed to improve the performance of P. aeruginosa-inoculated MFC. With an aerobic start-up and following an anaerobic discharge process, the current density of MFC reached a maximum of 99.80µA/cm , which was 91.6% higher than the MFC with conventional constant-anaerobic operation. Cyclic voltammetry and HPLC analysis showed that aerobic start-up significantly increased electron shuttle (pyocyanin) production (76% higher than the constant-anaerobic MFC). Additionally, enhanced anode biofilm formation was also observed in the integrated aerobic-anaerobic MFC. The increased pyocyanin production and biofilm formation promoted extracellular electron transfer from EAB to the anode and were the underlying mechanism for the MFC performance enhancement. This work demonstrated the integrated aerobic-anaerobic strategy would be a practical strategy to enhance the electricity generation of MFC.
[Mh] Termos MeSH primário: Fontes de Energia Bioelétrica
Pseudomonas aeruginosa
[Mh] Termos MeSH secundário: Eletricidade
Eletrodos
Piocianina
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
9OQM399341 (Pyocyanine)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170626
[St] Status:MEDLINE


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[PMID]:28582765
[Au] Autor:Yu D; Yong YC; Liu C; Fang Y; Bai L; Dong S
[Ad] Endereço:State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Science, 5625 Renmin Street, Changchun 130022, Jilin Province, PR China.
[Ti] Título:New applications of genetically modified Pseudomonas aeruginosa for toxicity detection in water.
[So] Source:Chemosphere;184:106-111, 2017 Oct.
[Is] ISSN:1879-1298
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A novel mediator-free method based on genetically modified bacteria was developed for detecting water toxicity, where genetically modified Pseudomonas aeruginosa (GM P. aeruginosa) was selected as the biosensor strain and pyocyanin (PYO) produced by this strain was used as the indicator. The toxicity response of GM P. aeruginosa to 3, 5-dichlorophenol (3, 5-DCP) was measured electrochemically and spectroscopically, and the half maximal inhibitory concentration (IC ) of 3, 5-DCP was determined to be 15.1 mg/L. Strikingly, the toxicity of sample solution with 3, 5-DCP could also be estimated visually by naked eyes at a concentration as low as 10 mg/L. The present study provided a convenient, sensitive and cost-effective method for water toxicity detection, and extended biosensing application of the genetically modified bacterium.
[Mh] Termos MeSH primário: Pseudomonas aeruginosa/genética
Testes de Toxicidade/métodos
Poluentes da Água/toxicidade
[Mh] Termos MeSH secundário: Bactérias
Técnicas Biossensoriais
Organismos Geneticamente Modificados
Piocianina
Poluentes da Água/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Water Pollutants); 9OQM399341 (Pyocyanine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170606
[St] Status:MEDLINE


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[PMID]:28421612
[Au] Autor:Tiwary BK; Ghosh R; Moktan S; Ranjan VK; Dey P; Choudhury D; Dutta S; Deb D; Das AP; Chakraborty R
[Ad] Endereço:Omics Laboratory, Department of Biotechnology, University of North Bengal, Siliguri, India.
[Ti] Título:Prospective bacterial quorum sensing inhibitors from Indian medicinal plant extracts.
[So] Source:Lett Appl Microbiol;65(1):2-10, 2017 Jul.
[Is] ISSN:1472-765X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:As virulence of many pathogenic bacteria is regulated by the phenomenon of quorum sensing (QS), the present study aimed to find the QS-inhibiting (QS-I) property (if any) in 61 Indian medicinal plants. The presence of QS-I compound in the leaf extract was evaluated by its ability to inhibit production of pigment in Chromobacterium violaceum MTCC 2656 (violacein) and Pseudomonas aeruginosa MTCC 2297 (pyocyanin) or swarming of P. aeruginosa MTCC 2297. Extracts of three plants, Astilbe rivularis, Fragaria nubicola and Osbeckia nepalensis, have shown a dose-dependent inhibition of violacein production with no negative effect on bacterial growth. Inhibition of pyocyanin pigment production and swarming motility in P. aeruginosa MTCC 2297 was also shown. Based on the results obtained by gas chromatography-mass spectroscopy (GC-MS) and thin-layer chromatography-direct bioautography (TLC-DB), it was concluded that triterpenes and flavonoid compounds found in the three plant extracts could have QS-I activity. SIGNIFICANCE AND IMPACT OF THE STUDY: A novel alternative prospect to prevent bacterial infections without inhibiting the growth is to apply chemicals that inhibit quorum sensing mechanism of the pathogens. Antiquorum property of 61 medicinal plants was evaluated by the ability of their leaf extract(s) to inhibit production of pigment (violacein in Chromobacterium violaceum MTCC 2656, pyocyanin in Pseudomonas aeruginosa MTCC 2297) or swarming in P. aeruginosa MTCC 2297. The most prospective plants (for the development of quorum sensing inhibitor), showing inhibition of violacein production without affecting bacterial growth, were Astilbe rivularis, Fragaria nubicola and Osbeckia nepalensis.
[Mh] Termos MeSH primário: Chromobacterium/efeitos dos fármacos
Flavonoides/farmacologia
Indóis/metabolismo
Pseudomonas aeruginosa/efeitos dos fármacos
Piocianina/biossíntese
Percepção de Quorum/efeitos dos fármacos
Triterpenos/farmacologia
[Mh] Termos MeSH secundário: Antibacterianos/farmacologia
Fragaria/química
Medicina Tradicional
Melastomataceae/química
Extratos Vegetais/farmacologia
Folhas de Planta/química
Plantas Medicinais/química
Estudos Prospectivos
Saxifragaceae/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Flavonoids); 0 (Indoles); 0 (Plant Extracts); 0 (Triterpenes); 9OQM399341 (Pyocyanine); QJH0DSQ3SG (violacein)
[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:170420
[St] Status:MEDLINE
[do] DOI:10.1111/lam.12748


  6 / 428 MEDLINE  
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[PMID]:28333255
[Au] Autor:Iiyama K; Takahashi E; Lee JM; Mon H; Morishita M; Kusakabe T; Yasunaga-Aoki C
[Ad] Endereço:Laboratory of Insect Pathology and Microbial Control, Institute of Biological Control, Faculty of Agriculture, Graduate School, Kyushu University, Fukuoka 812-8581, Japan.
[Ti] Título:Alkaline protease contributes to pyocyanin production in Pseudomonas aeruginosa.
[So] Source:FEMS Microbiol Lett;364(7), 2017 Apr 01.
[Is] ISSN:1574-6968
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The role of the alkaline protease (AprA) in pyocyanin production in Pseudomonas aeruginosa was investigated. AprA was overproduced when a plasmid carrying the aprA gene was introduced to an aprA-deletion mutant strain, EG03; thus, aprA-complemented EG03 was used as an overproducing strain. The complemented strain produced higher pyocyanin than the mutant strain in all commercially available media evaluated. Particularly, pyocyanin production was higher in the complemented than in the parental strain in brain-heart infusion and tryptic soy broths. These results suggested that protein degradation products by AprA were utilized for pyocyanin production. Protein-rich media were used in subsequent validation studies. Similar results were obtained when the basal medium was supplemented with casein or skim milk as the sole organic nitrogen source. However, gelatin failed to induce abundant pyocyanin production in the complemented strain, despite the presence of protein degradation products by AprA as assessed by SDS-PAGE. Thus, gelatin degradation products may not be suitable for pyocyanin synthesis. In conclusion, AprA could contribute to pyocyanin production in the presence of several proteins or peptides.
[Mh] Termos MeSH primário: Proteínas de Bactérias/metabolismo
Endopeptidases/metabolismo
Pseudomonas aeruginosa/enzimologia
Piocianina/biossíntese
[Mh] Termos MeSH secundário: Animais
Proteínas de Bactérias/genética
Caseínas/metabolismo
Caseínas/farmacologia
Meios de Cultura/química
Eletroforese em Gel de Poliacrilamida
Endopeptidases/genética
Gelatina/metabolismo
Teste de Complementação Genética
Leite/metabolismo
Proteólise
Pseudomonas aeruginosa/genética
Pseudomonas aeruginosa/patogenicidade
Fatores de Virulência/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Caseins); 0 (Culture Media); 0 (Virulence Factors); 9000-70-8 (Gelatin); 9OQM399341 (Pyocyanine); EC 3.4.- (Endopeptidases); EC 3.4.99.- (alkaline protease)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170526
[Lr] Data última revisão:
170526
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170324
[St] Status:MEDLINE
[do] DOI:10.1093/femsle/fnx051


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[PMID]:28158967
[Au] Autor:O'Brien S; Williams D; Fothergill JL; Paterson S; Winstanley C; Brockhurst MA
[Ad] Endereço:Department of Biology, University of York, Wentworth Way, York, YO10 5DD, UK. siobhan.obrien@york.ac.uk.
[Ti] Título:High virulence sub-populations in Pseudomonas aeruginosa long-term cystic fibrosis airway infections.
[So] Source:BMC Microbiol;17(1):30, 2017 Feb 03.
[Is] ISSN:1471-2180
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Pseudomonas aeruginosa typically displays loss of virulence-associated secretions over the course of chronic cystic fibrosis infections. This has led to the suggestion that virulence is a costly attribute in chronic infections. However, previous reports suggest that overproducing (OP) virulent pathotypes can coexist with non-producing mutants in the CF lung for many years. The consequences of such within-patient phenotypic diversity for the success of this pathogen are not fully understood. Here, we provide in-depth quantification of within-host variation in the production of three virulence associated secretions in the Liverpool cystic fibrosis epidemic strain of P. aeruginosa, and investgate the effect of this phenotypic variation on virulence in acute infections of an insect host model. RESULTS: Within-patient variation was present for all three secretions (pyoverdine, pyocyanin and LasA protease). In two out of three patients sampled, OP isolates coexisted with under-producing mutants. In the third patient, all 39 isolates were under-producers of all three secretions relative to the transmissible ancestor LESB58. Finally, this phenotypic variation translated into variation in virulence in an insect host model. CONCLUSIONS: Within population variation in the production of P. aeruginosa virulence-associated secretions can lead to high virulence sub-populations persisting in patients with chronic CF infections.
[Mh] Termos MeSH primário: Fibrose Cística/complicações
Pulmão/microbiologia
Infecções por Pseudomonas/etiologia
Pseudomonas aeruginosa/patogenicidade
Virulência
[Mh] Termos MeSH secundário: Adulto
Animais
Proteínas de Bactérias/genética
Doença Crônica
Modelos Animais de Doenças
Feminino
Seres Humanos
Insetos/microbiologia
Metaloproteases/análise
Metaloproteases/secreção
Mutação
Oligopeptídeos/análise
Oligopeptídeos/secreção
Fenótipo
Pneumonia Bacteriana/etiologia
Piocianina/análise
Piocianina/secreção
Fatores de Virulência/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Oligopeptides); 0 (Virulence Factors); 8062-00-8 (pyoverdin); 9OQM399341 (Pyocyanine); EC 3.4.- (LasA protein, Pseudomonas aeruginosa); EC 3.4.- (Metalloproteases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170205
[St] Status:MEDLINE
[do] DOI:10.1186/s12866-017-0941-6


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[PMID]:28094526
[Au] Autor:Chen T; Sheng J; Fu Y; Li M; Wang J; Jia AQ
[Ad] Endereço:School of Environmental and Biological Engineering, Nanjing University of Science and Technology , Xiao Ling Wei No. 200, Nanjing 210094, China.
[Ti] Título:H NMR-Based Global Metabolic Studies of Pseudomonas aeruginosa upon Exposure of the Quorum Sensing Inhibitor Resveratrol.
[So] Source:J Proteome Res;16(2):824-830, 2017 Feb 03.
[Is] ISSN:1535-3907
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Quorum sensing (QS) is a process of bacterial communication that has been a novel target for drug discovery. Pyocyanin quantification assay confirmed that resveratrol was an effective quorum sensing inhibitor (QSI) against Pseudomonas aeruginosa PAO1. In this study, the global metabolite changes of P. aeruginosa PAO1 exposed to QSI resveratrol were investigated by H NMR spectroscopy. A total of 40 metabolites containing amino acids, organic acid, organic amine, and energy storage compounds were identified. The changed metabolic profile indicated that resveratrol influenced pathways including oxidative stress, protein synthesis, and energy metabolism. Oxidative stress could upregulate the expression of genes related to QS in P. aeruginosa. It suggested that resveratrol could inhibit the QS systems in P. aeruginosa PAO1 by relieving oxidative stress due to its antioxidant activity. On the other hand, resveratrol could attenuate the pathogenicity of P. aeruginosa PAO1 by disturbing the TCA cycle so that anaerobic respiration could suppress the virulence because anaerobiosis could induce the loss of cytotoxicity regulated by QS in P. aeruginosa. These findings deepened our comprehending of the metabolic responses of P. aeruginosa PAO1 to resveratrol and pinpointed the possible underlying mechanism of resveratrol's inhibition effect on QS in P. aeruginosa PAO1.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Biofilmes/efeitos dos fármacos
Regulação Bacteriana da Expressão Gênica
Pseudomonas aeruginosa/efeitos dos fármacos
Percepção de Quorum/efeitos dos fármacos
Estilbenos/farmacologia
[Mh] Termos MeSH secundário: Antibacterianos/isolamento & purificação
Ciclo do Ácido Cítrico/efeitos dos fármacos
Glicólise/efeitos dos fármacos
Redes e Vias Metabólicas/efeitos dos fármacos
Redes e Vias Metabólicas/genética
Metabolômica
Ressonância Magnética Nuclear Biomolecular
Estresse Oxidativo
Extratos Vegetais/química
Biossíntese de Proteínas/efeitos dos fármacos
Pseudomonas aeruginosa/genética
Pseudomonas aeruginosa/metabolismo
Piocianina/antagonistas & inibidores
Piocianina/biossíntese
Smilax/química
Estilbenos/isolamento & purificação
Fatores de Virulência/antagonistas & inibidores
Fatores de Virulência/biossíntese
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Plant Extracts); 0 (Stilbenes); 0 (Virulence Factors); 9OQM399341 (Pyocyanine); Q369O8926L (resveratrol)
[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:170118
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jproteome.6b00800


  9 / 428 MEDLINE  
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[PMID]:27940577
[Au] Autor:Costa KC; Glasser NR; Conway SJ; Newman DK
[Ad] Endereço:Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
[Ti] Título:Pyocyanin degradation by a tautomerizing demethylase inhibits Pseudomonas aeruginosa biofilms.
[So] Source:Science;355(6321):170-173, 2017 01 13.
[Is] ISSN:1095-9203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The opportunistic pathogen Pseudomonas aeruginosa produces colorful redox-active metabolites called phenazines, which underpin biofilm development, virulence, and clinical outcomes. Although phenazines exist in many forms, the best studied is pyocyanin. Here, we describe pyocyanin demethylase (PodA), a hitherto uncharacterized protein that oxidizes the pyocyanin methyl group to formaldehyde and reduces the pyrazine ring via an unusual tautomerizing demethylation reaction. Treatment with PodA disrupts P. aeruginosa biofilm formation similarly to DNase, suggesting interference with the pyocyanin-dependent release of extracellular DNA into the matrix. PodA-dependent pyocyanin demethylation also restricts established biofilm aggregate populations experiencing anoxic conditions. Together, these results show that modulating extracellular redox-active metabolites can influence the fitness of a biofilm-forming microorganism.
[Mh] Termos MeSH primário: Proteínas de Bactérias/química
Proteínas de Bactérias/farmacologia
Biofilmes/efeitos dos fármacos
Mycobacterium fortuitum/enzimologia
Oxirredutases N-Desmetilantes/química
Oxirredutases N-Desmetilantes/farmacologia
Pseudomonas aeruginosa/efeitos dos fármacos
Piocianina/química
[Mh] Termos MeSH secundário: Cristalografia por Raios X
DNA/química
Metilação
Oxirredução
Pseudomonas aeruginosa/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Bacterial Proteins); 9007-49-2 (DNA); 9OQM399341 (Pyocyanine); EC 1.5.- (Oxidoreductases, N-Demethylating)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171005
[Lr] Data última revisão:
171005
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161213
[St] Status:MEDLINE
[do] DOI:10.1126/science.aag3180


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[PMID]:27933456
[Au] Autor:Sunder AV; Utari PD; Ramasamy S; van Merkerk R; Quax W; Pundle A
[Ad] Endereço:Division of Biochemical Sciences, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune, 411008, India.
[Ti] Título:Penicillin V acylases from gram-negative bacteria degrade N-acylhomoserine lactones and attenuate virulence in Pseudomonas aeruginosa.
[So] Source:Appl Microbiol Biotechnol;101(6):2383-2395, 2017 Mar.
[Is] ISSN:1432-0614
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Virulence pathways in gram-negative pathogenic bacteria are regulated by quorum sensing mechanisms, through the production and sensing of N-acylhomoserine lactone (AHL) signal molecules. Enzymatic degradation of AHLs leading to attenuation of virulence (quorum quenching) could pave the way for the development of new antibacterials. Penicillin V acylases (PVAs) belong to the Ntn hydrolase superfamily, together with AHL acylases. PVAs are exploited widely in the pharmaceutical industry, but their role in the natural physiology of their native microbes is not clearly understood. This report details the characterization of AHL degradation activity by homotetrameric PVAs from two gram-negative plant pathogenic bacteria, Pectobacterium atrosepticum (PaPVA) and Agrobacterium tumefaciens (AtPVA). Both the PVAs exhibited substrate specificity for degrading long-chain AHLs. Exogenous addition of these enzymes into Pseudomonas aeruginosa greatly diminished the production of elastase and pyocyanin and biofilm formation and increased the survival rate in an insect model of acute infection. Subtle structural differences in the PVA active site that regulate specificity for acyl chain length have been characterized, which could reflect the evolution of AHL-degrading acylases in relation to the environment of the bacteria that produce them and also provide strategies for enzyme engineering. The potential for using these enzymes as therapeutic agents in clinical applications and a few ideas about their possible significance in microbial physiology have also been discussed.
[Mh] Termos MeSH primário: Acil-Butirolactonas/química
Proteínas de Bactérias/química
Regulação Bacteriana da Expressão Gênica
Penicilina Amidase/química
Pseudomonas aeruginosa/genética
Pseudomonas aeruginosa/patogenicidade
[Mh] Termos MeSH secundário: Acil-Butirolactonas/metabolismo
Agrobacterium tumefaciens/enzimologia
Agrobacterium tumefaciens/genética
Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Biofilmes/crescimento & desenvolvimento
Domínio Catalítico
Clonagem Molecular
Escherichia coli/genética
Escherichia coli/metabolismo
Hidrólise
Modelos Moleculares
Elastase Pancreática/biossíntese
Pectobacterium/enzimologia
Pectobacterium/genética
Penicilina Amidase/genética
Penicilina Amidase/metabolismo
Conformação Proteica
Pseudomonas aeruginosa/metabolismo
Piocianina/biossíntese
Percepção de Quorum
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Especificidade por Substrato
Virulência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acyl-Butyrolactones); 0 (Bacterial Proteins); 0 (Recombinant Proteins); 9OQM399341 (Pyocyanine); EC 3.4.21.36 (Pancreatic Elastase); EC 3.5.1.11 (Penicillin Amidase)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170307
[Lr] Data última revisão:
170307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161210
[St] Status:MEDLINE
[do] DOI:10.1007/s00253-016-8031-5



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