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Pesquisa : D12.125.526 [Categoria DeCS]
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[PMID]:28466892
[Au] Autor:Bondí R; Longo F; Messina M; D'Angelo F; Visca P; Leoni L; Rampioni G
[Ad] Endereço:Department of Science, University Roma Tre, Rome, Italy. giordano.rampioni@uniroma3.it.
[Ti] Título:The multi-output incoherent feedforward loop constituted by the transcriptional regulators LasR and RsaL confers robustness to a subset of quorum sensing genes in Pseudomonas aeruginosa.
[So] Source:Mol Biosyst;13(6):1080-1089, 2017 Jun 01.
[Is] ISSN:1742-2051
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Quorum sensing (QS) is an intercellular communication system which controls virulence-related phenotypes in the human pathogen Pseudomonas aeruginosa. LasR is the QS receptor protein which responds to the signal molecule N-(3-oxododecanoyl)homoserine lactone (3OC -HSL) and promotes signal production by increasing the transcription of the 3OC -HSL synthase gene, lasI. LasR also activates the expression of other genes, including rsaL, coding for the RsaL protein which acts as a transcriptional repressor of lasI. Direct gene activation and RsaL-mediated gene repression, both exerted by LasR on the expression of the output gene lasI, generate a regulatory network motif known as the type 1 incoherent feedforward loop (IFFL-1) that governs 3OC -HSL production. In addition to lasI, RsaL directly represses a set of LasR-activated genes; hence, the IFFL-1 generated by LasR and RsaL is a multi-output IFFL-1. Here we demonstrate that the multi-output IFFL-1 constituted by LasR and RsaL confers robustness with respect to fluctuations in the levels of LasR to the phenotypes controlled by both these transcriptional regulators (e.g. 3OC -HSL synthesis and pyocyanin production). In contrast, other virulence-related phenotypes controlled by LasR but not by RsaL (e.g. elastase and protease production) are sensitive to changes in LasR levels. Overall, the multi-output IFFL-1 generated by LasR and RsaL splits the QS regulon into two distinct sub-regulons with different robustness with respect to LasR fluctuations. This emerging regulatory property enhances the phenotypic plasticity of P. aeruginosa, thus contributing to its adaptation to changing environments.
[Mh] Termos MeSH primário: Proteínas de Bactérias/metabolismo
Pseudomonas aeruginosa/metabolismo
Pseudomonas aeruginosa/fisiologia
Percepção de Quorum
Proteínas Repressoras/metabolismo
Transativadores/metabolismo
[Mh] Termos MeSH secundário: 4-Butirolactona/análogos & derivados
4-Butirolactona/metabolismo
Proteínas de Bactérias/genética
Regulação da Expressão Gênica
Homosserina/análogos & derivados
Homosserina/metabolismo
Proteínas Repressoras/genética
Transativadores/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (LasR protein, Pseudomonas aeruginosa); 0 (N-(3-oxododecanoyl)homoserine lactone); 0 (Repressor Proteins); 0 (Trans-Activators); 0 (rsaL protein, Pseudomonas aeruginosa); 1192-20-7 (homoserine lactone); 6KA95X0IVO (Homoserine); OL659KIY4X (4-Butyrolactone)
[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:170504
[St] Status:MEDLINE
[do] DOI:10.1039/c7mb00040e


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[PMID]:29427588
[Au] Autor:Nishimura-Danjobara Y; Oyama K; Yokoigawa K; Oyama Y
[Ad] Endereço:Department of Food Science, Faculty of Bioscience and Bioindustry, Tokushima University, Tokushima 770-8513, Japan.
[Ti] Título:Hyperpolarization by N-(3-oxododecanoyl)-l-homoserine-lactone, a quorum sensing molecule, in rat thymic lymphocytes.
[So] Source:Chem Biol Interact;283:91-96, 2018 Mar 01.
[Is] ISSN:1872-7786
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:To study the adverse effects of N-(3-oxododecanoyl)-l-homoserine-lactone (ODHL), a quorum sensing molecule, on mammalian host cells, its effect on membrane potential was examined in rat thymic lymphocytes using flow cytometric techniques with a voltage-sensitive fluorescent probe. As 3-300 µM ODHL elicited hyperpolarization, it is likely that it increases membrane K permeability because hyperpolarization is directly linked to changing K gradient across membranes, but not Na and Cl gradients. ODHL did not increase intracellular Ca concentration. ODHL also produced a response in the presence of an intracellular Zn chelator. Thus, it is unlikely that intracellular Ca and Zn are attributed to the response. Quinine, a non-specific K channel blocker, greatly reduced hyperpolarization. However, because charybdotoxin, tetraethylammonium chloride, 4-aminopyridine, and glibenclamide did not affect it, it is pharmacologically hypothesized that Ca -activated K channels, voltage-gated K channels, and ATP-sensitive K channels are not involved in ODHL-induced hyperpolarization. Although the K channels responsible for ODHL-induced hyperpolarization have not been identified, it is suggested that ODHL can elicit hyperpolarization in mammalian host cells, disturbing cellular functions.
[Mh] Termos MeSH primário: 4-Butirolactona/análogos & derivados
Polaridade Celular/efeitos dos fármacos
Homosserina/análogos & derivados
Percepção de Quorum/efeitos dos fármacos
[Mh] Termos MeSH secundário: 4-Butirolactona/farmacologia
Animais
Cálcio/metabolismo
Charibdotoxina/farmacologia
Citometria de Fluxo
Glibureto/farmacologia
Homosserina/farmacologia
Canais KATP/metabolismo
Linfócitos/citologia
Linfócitos/efeitos dos fármacos
Linfócitos/metabolismo
Permeabilidade/efeitos dos fármacos
Potássio/metabolismo
Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo
Quinina/farmacologia
Ratos
Ratos Wistar
Timócitos/citologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (KATP Channels); 0 (N-(3-oxododecanoyl)homoserine lactone); 0 (Potassium Channels, Voltage-Gated); 115422-61-2 (Charybdotoxin); 6KA95X0IVO (Homoserine); A7V27PHC7A (Quinine); OL659KIY4X (4-Butyrolactone); RWP5GA015D (Potassium); SX6K58TVWC (Glyburide); SY7Q814VUP (Calcium)
[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:180211
[St] Status:MEDLINE


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[PMID]:29223568
[Au] Autor:Nishimura-Danjobara Y; Oyama K; Kanemaru K; Takahashi K; Yokoigawa K; Oyama Y
[Ad] Endereço:Department of Food Science, Faculty of Bioscience and Bioindustry, Tokushima University, Tokushima 770-8513, Japan.
[Ti] Título:N-(3-oxododecanoyl)-l-homoserine-lactone, a quorum sensing molecule, affects cellular content of nonprotein thiol content in rat lymphocytes: Its relation with intracellular Zn .
[So] Source:Chem Biol Interact;280:28-32, 2018 Jan 25.
[Is] ISSN:1872-7786
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Cellular actions of N-(3-oxododecanoyl)-l-homoserine-lactone (ODHL), a quorum sensing molecule of bacteria, were studied on rat thymocytes using a flow cytometer with appropriate fluorescent dyes to elucidate the effects of ODHL on host cells. A bell-shaped concentration-response relation was observed in the ODHL-induced changes in cellular glutathione content ([GSH]i). ODHL concentration-dependently increased intracellular Zn levels ([Zn ]i) and cellular O content ([O ]i). The bell-shaped relation induced by ODHL can be explained as follows: a low concentration of ODHL is expected to induce moderate oxidative stress that intracellularly releases Zn by converting thiols to disulfides. A slight elevation of [Zn ]i may increase the [GSH]i. On the other hand, it is likely that a high concentration of ODHL causes severe oxidative stress that further causes both the decrease in [GSH]i and the increase in [Zn ]i. Excessive increase in [Zn ]i may augment oxidative stress that further decreases the [GSH]i. Other notable actions induced by ODHL included the elevation of [Zn ]i by Zn influx and the increase in [GSH]i under Zn -free conditions. Therefore, it is suggested that ODHL elicits diverse actions on host cells.
[Mh] Termos MeSH primário: 4-Butirolactona/análogos & derivados
Homosserina/análogos & derivados
Estresse Oxidativo/efeitos dos fármacos
Compostos de Sulfidrila/metabolismo
Zinco/metabolismo
[Mh] Termos MeSH secundário: 4-Butirolactona/farmacologia
Animais
Apoptose/efeitos dos fármacos
Células Cultivadas
Glutationa/metabolismo
Homosserina/farmacologia
Linfócitos/citologia
Linfócitos/efeitos dos fármacos
Linfócitos/metabolismo
Masculino
Percepção de Quorum/efeitos dos fármacos
Ratos
Ratos Wistar
Timo/citologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (N-(3-oxododecanoyl)homoserine lactone); 0 (Sulfhydryl Compounds); 6KA95X0IVO (Homoserine); GAN16C9B8O (Glutathione); J41CSQ7QDS (Zinc); OL659KIY4X (4-Butyrolactone)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180129
[Lr] Data última revisão:
180129
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171211
[St] Status:MEDLINE


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[PMID]:28692660
[Au] Autor:Balhouse BN; Patterson L; Schmelz EM; Slade DJ; Verbridge SS
[Ad] Endereço:School of Biomedical Engineering and Sciences, Virginia Tech-Wake Forest University, Blacksburg, VA, United States of America.
[Ti] Título:N-(3-oxododecanoyl)-L-homoserine lactone interactions in the breast tumor microenvironment: Implications for breast cancer viability and proliferation in vitro.
[So] Source:PLoS One;12(7):e0180372, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:It is well documented that the tumor microenvironment profoundly impacts the etiology and progression of breast cancer, yet the contribution of the resident microbiome within breast tissue remains poorly understood. Tumor microenvironmental conditions, such as hypoxia and dense tumor stroma, predispose progressive phenotypes and therapy resistance, however the role of bacteria in this interplay remains uncharacterized. We hypothesized that the effect of individual bacterial secreted molecules on breast cancer viability and proliferation would be modulated by these tumor-relevant stressors differentially for cells at varying stages of progression. To test this, we incubated human breast adenocarcinoma cells (MDA-MB-231, MCF-DCIS.com) and non-malignant breast epithelial cells (MCF-10A) with N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL), a quorum-sensing molecule from Pseudomonas aeruginosa that regulates bacterial stress responses. This molecule was selected because Pseudomonas was recently characterized as a significant fraction of the breast tissue microbiome and OdDHL is documented to impact mammalian cell viability. After OdDHL treatment, we demonstrated the greatest decrease in viability with the more malignant MDA-MB-231 cells and an intermediate MCF-DCIS.com (ductal carcinoma in situ) response. The responses were also culture condition (i.e. microenvironment) dependent. These results contrast the MCF-10A response, which demonstrated no change in viability in any culture condition. We further determined that the observed trends in breast cancer viability were due to modulation of proliferation for both cell types, as well as the induction of necrosis for MDA-MB-231 cells in all conditions. Our results provide evidence that bacterial quorum-sensing molecules interact with the host tissue environment to modulate breast cancer viability and proliferation, and that the effect of OdDHL is dependent on both cell type as well as microenvironment. Understanding the interactions between bacterial signaling molecules and the host tissue environment will allow for future studies that determine the contribution of bacteria to the onset, progression, and therapy response of breast cancer.
[Mh] Termos MeSH primário: 4-Butirolactona/análogos & derivados
Neoplasias da Mama/patologia
Homosserina/análogos & derivados
Microambiente Tumoral/efeitos dos fármacos
[Mh] Termos MeSH secundário: 4-Butirolactona/farmacologia
Hipóxia Celular/efeitos dos fármacos
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Feminino
Homosserina/farmacologia
Seres Humanos
Necrose
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (N-(3-oxododecanoyl)homoserine lactone); 6KA95X0IVO (Homoserine); OL659KIY4X (4-Butyrolactone)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171025
[Lr] Data última revisão:
171025
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170711
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0180372


  5 / 1077 MEDLINE  
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[PMID]:28675039
[Au] Autor:Sagong HY; Kim KJ
[Ad] Endereço:KNU Creative BioResearch Group, School of Life Sciences, Kyungpook National University , Daehak-ro 80, Buk-ku, Daegu 702-701, Korea.
[Ti] Título:Structural Insights into Substrate Specificity of Cystathionine γ-Synthase from Corynebacterium glutamicum.
[So] Source:J Agric Food Chem;65(29):6002-6008, 2017 Jul 26.
[Is] ISSN:1520-5118
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cystathionine γ-synthase (MetB) condenses O-acetyl-l-homoserine (OAHS) or O-succinyl-l-homoserine (OSHS) with cysteine to produce cystathionine. To investigate the molecular mechanisms and substrate specificity of MetB from Corynebacterium glutamicum (CgMetB), we determined its crystal structure at 1.5 Å resolution. The pyridoxal phosphate cofactor is covalently bound to Lys204 via a Schiff base linkage in the deep cavity. Superposition with the structure of MetB from Nicotiana tabacum in complex with its inhibitor dl-(E)-2-amino-5-phosphono-3-pentenoic acid revealed that Thr347 from the ß10-ß11 connecting loop, located at the entrance of the active site, is speculated to be a main contributor for stabilization of the acetyl group of OAHS. Moreover, on the basis of structural comparison of CgMetB with EcMetB utilizing OSHS as a main substrate, we propose that the conformation of the ß10-ß11 connecting loops determines the size and shape of the acetyl- or succinyl-group binding site and ultimately determines the substrate specificity of MetBs toward OAHS or OSHS.
[Mh] Termos MeSH primário: Proteínas de Bactérias/química
Carbono-Oxigênio Liases/química
Corynebacterium glutamicum/enzimologia
[Mh] Termos MeSH secundário: Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Sítios de Ligação
Carbono-Oxigênio Liases/genética
Carbono-Oxigênio Liases/metabolismo
Domínio Catalítico
Corynebacterium glutamicum/química
Corynebacterium glutamicum/genética
Homosserina/análogos & derivados
Homosserina/química
Homosserina/metabolismo
Cinética
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 1492-23-5 (O-succinylhomoserine); 6KA95X0IVO (Homoserine); EC 2.5.1.48 (O-succinylhomoserine (thiol)-lyase); EC 4.2.- (Carbon-Oxygen Lyases)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170809
[Lr] Data última revisão:
170809
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170705
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jafc.7b02391


  6 / 1077 MEDLINE  
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[PMID]:28614901
[Au] Autor:Kim Y; Chhor G; Tsai CS; Fox G; Chen CS; Winans NJ; Jedrzejczak R; Joachimiak A; Winans SC
[Ad] Endereço:Midwest Center for Structural Genomics, Biosciences, Argonne National Laboratory, Argonne, Illinois, 60439.
[Ti] Título:X-ray crystal structures of the pheromone-binding domains of two quorum-hindered transcription factors, YenR of Yersinia enterocolitica and CepR2 of Burkholderia cenocepacia.
[So] Source:Proteins;85(10):1831-1844, 2017 Oct.
[Is] ISSN:1097-0134
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The ability of LuxR-type proteins to regulate transcription is controlled by bacterial pheromones, N-acylhomoserine lactones (AHLs). Most LuxR-family proteins require their cognate AHLs for activity, and some of them require AHLs for folding and stability, and for protease-resistance. However, a few members of this family are able to fold, dimerize, bind DNA, and regulate transcription in the absence of AHLs; moreover, these proteins are antagonized by their cognate AHLs. One such protein is YenR of Yersinia enterocolitica, which is antagonized by N-3-oxohexanoyl-l-homoserine lactone (OHHL). This pheromone is produced by the OHHL synthase, a product of the adjacent yenI gene. Another example is CepR2 of Burkholderia cenocepacia, which is antagonized by N-octanoyl-l-homoserine lactone (OHL), whose synthesis is directed by the cepI gene of the same bacterium. Here, we describe the high-resolution crystal structures of the AHL binding domains of YenR and CepR2. YenR was crystallized in the presence and absence of OHHL. While this ligand does not cause large scale changes in the YenR structure, it does alter the orientation of several highly conserved YenR residues within and near the pheromone-binding pocket, which in turn caused a significant movement of a surface-exposed loop.
[Mh] Termos MeSH primário: Proteínas de Bactérias/química
Homosserina/análogos & derivados
Lactonas/química
Transativadores/química
[Mh] Termos MeSH secundário: Proteínas de Bactérias/genética
Burkholderia cenocepacia/química
Cristalografia por Raios X
Proteínas de Ligação a DNA/química
Regulação Bacteriana da Expressão Gênica
Homosserina/química
Feromônios/química
Conformação Proteica
Domínios Proteicos/genética
Dobramento de Proteína
Transativadores/genética
Fatores de Transcrição/química
Yersinia enterocolitica/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (CepR protein, Burkholderia); 0 (DNA-Binding Proteins); 0 (Lactones); 0 (N-octanoylhomoserine lactone); 0 (Pheromones); 0 (Trans-Activators); 0 (Transcription Factors); 0 (YenR protein, Yersinia enterocolitica); 6KA95X0IVO (Homoserine)
[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:170615
[St] Status:MEDLINE
[do] DOI:10.1002/prot.25336


  7 / 1077 MEDLINE  
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[PMID]:28554093
[Au] Autor:Park JS; Ryu EJ; Li L; Choi BK; Kim BM
[Ad] Endereço:Department of Chemistry, College of Natural Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.
[Ti] Título:New bicyclic brominated furanones as potent autoinducer-2 quorum-sensing inhibitors against bacterial biofilm formation.
[So] Source:Eur J Med Chem;137:76-87, 2017 Sep 08.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Bacterial behaviors such as virulence factor secretion and biofilm formation are critical for survival, and are effectively regulated through quorum sensing, a mechanism of intra- and interspecies communication in response to changes in cell density and species complexity. Many bacterial species colonize host tissues and form a defensive structure called a biofilm, which can be the basis of inflammatory diseases. Periodontitis, a chronic inflammatory disease affecting the periodontium, is caused by subgingival biofilms related to periodontopathogens. In particular, Fusobacterium nucleatum is a major co-aggregation bridge organism in the formation and growth of subgingival biofilms, linking the early and late colonizers in periodontal biofilms. According to our previous study, the intergeneric quorum-sensing signal molecule autoinducer-2 (AI-2) of F. nucleatum plays a key role in intra- and interspecies interactions of periodontopathogens, and may be a good target for periodontal biofilm inhibition. Recently, brominated furanones produced by the macroalga Delisea pulchra were shown to inhibit biofilm formation via AI-2, and have been investigated toward the goal of increasing the inhibition effect. In this study, we describe the synthesis of new bromofuranone analogs, i.e., 3-(dibromomethylene)isobenzofuran-1(3H)-one derivatives, and demonstrate their inhibitory activities against biofilm formation by periodontopathogens, including F. nucleatum, Porphyromonas gingivalis, and Tannerella forsythia.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Biofilmes/efeitos dos fármacos
Furanos/farmacologia
Homosserina/análogos & derivados
Lactonas/antagonistas & inibidores
[Mh] Termos MeSH secundário: Antibacterianos/síntese química
Antibacterianos/química
Relação Dose-Resposta a Droga
Furanos/síntese química
Fusobacterium nucleatum/efeitos dos fármacos
Homosserina/antagonistas & inibidores
Testes de Sensibilidade Microbiana
Estrutura Molecular
Porphyromonas gingivalis/efeitos dos fármacos
Percepção de Quorum/efeitos dos fármacos
Relação Estrutura-Atividade
Tannerella forsythia/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Furans); 0 (Lactones); 0 (N-octanoylhomoserine lactone); 6KA95X0IVO (Homoserine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170920
[Lr] Data última revisão:
170920
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170530
[St] Status:MEDLINE


  8 / 1077 MEDLINE  
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[PMID]:28552952
[Au] Autor:Hurley A; Bassler BL
[Ad] Endereço:Department of Molecular Biology, Princeton University, Princeton, NJ, United States of America.
[Ti] Título:Asymmetric regulation of quorum-sensing receptors drives autoinducer-specific gene expression programs in Vibrio cholerae.
[So] Source:PLoS Genet;13(5):e1006826, 2017 May.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Quorum sensing (QS) is a mechanism of chemical communication that bacteria use to monitor cell-population density and coordinate group behaviors. QS relies on the production, detection, and group-wide response to extracellular signal molecules called autoinducers. Vibrio cholerae employs parallel QS circuits that converge into a shared signaling pathway. At high cell density, the CqsS and LuxPQ QS receptors detect the intra-genus and inter-species autoinducers CAI-1 and AI-2, respectively, to repress virulence factor production and biofilm formation. We show that positive feedback, mediated by the QS pathway, increases CqsS but not LuxQ levels during the transition into QS-mode, which amplifies the CAI-1 input into the pathway relative to the AI-2 input. Asymmetric feedback on CqsS enables responses exclusively to the CAI-1 autoinducer. Because CqsS exhibits the dominant QS signaling role in V. cholerae, agonism of CqsS with synthetic compounds could be used to control pathogenicity and host dispersal. We identify nine compounds that share no structural similarity to CAI-1, yet potently agonize CqsS via inhibition of CqsS autokinase activity.
[Mh] Termos MeSH primário: Proteínas de Bactérias/metabolismo
Regulação Bacteriana da Expressão Gênica
Homosserina/análogos & derivados
Cetonas/metabolismo
Lactonas/metabolismo
Percepção de Quorum
Vibrio cholerae/metabolismo
[Mh] Termos MeSH secundário: Proteínas de Bactérias/genética
Retroalimentação Fisiológica
Homosserina/química
Homosserina/metabolismo
Cetonas/química
Lactonas/química
Vibrio cholerae/genética
Vibrio cholerae/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (3-hydroxytridecan-4-one); 0 (Bacterial Proteins); 0 (Ketones); 0 (Lactones); 0 (N-octanoylhomoserine lactone); 6KA95X0IVO (Homoserine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170530
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1006826


  9 / 1077 MEDLINE  
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[PMID]:28418096
[Au] Autor:Bao L; Yu J; Zhong H; Huang D; Lu Q
[Ad] Endereço:Department of Neonatology, Children's Hospital, Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing, China.
[Ti] Título:Expression of toll-like receptors in T lymphocytes stimulated with N-(3-oxododecanoyl)-L-homoserine lactone from Pseudomonas aeruginosa.
[So] Source:APMIS;125(6):553-557, 2017 Jun.
[Is] ISSN:1600-0463
[Cp] País de publicação:Denmark
[La] Idioma:eng
[Ab] Resumo:The establishment of chronic Pseudomonas aeruginosa infections is correlated with the disturbance of the host immune system. The P. aeruginosa quorum-sensing molecule N-3-(oxododecanoyl)-L-homoserine lactone (3-O-C12-HSL) has the potential to modulate the host immune system. The immune system recognizes pathogens via toll-like receptors (TLRs). We found that 3-O-C12-HSL induced TLR changes in monocytes. However, the role of T cells in P. aeruginosa infection has not been delineated. In order to understand this activity, we examined whether 3-O-C12-HSL has an effect on the immune function and the expression of TLRs in T lymphocytes. Human peripheral blood mononuclear cells (PBMCs) cells were cultured with 0, 1, 10, 50, or 100 µM 3-O-C12-HSL for 12 h. TLR2/TLR4 expression and T-lymphocyte proliferation were increased in a dose-dependent manner, and 100 µM 3-O-C12-HSL significantly increased TLR2 expression. Moreover, tumor necrosis factor-α production of these PBMCs was inhibited. To conclude, 3-O-C12-HSL can induce lymphocyte cell proliferation. These findings provide a new perspective on our understanding of the persistence of the chronic inflammation that accompanies P. aeruginosa infection.
[Mh] Termos MeSH primário: 4-Butirolactona/análogos & derivados
Expressão Gênica
Homosserina/análogos & derivados
Linfócitos T/efeitos dos fármacos
Linfócitos T/imunologia
Receptores Toll-Like/biossíntese
[Mh] Termos MeSH secundário: 4-Butirolactona/isolamento & purificação
4-Butirolactona/metabolismo
Proliferação Celular/efeitos dos fármacos
Células Cultivadas
Homosserina/isolamento & purificação
Homosserina/metabolismo
Seres Humanos
Fator de Necrose Tumoral alfa/secreção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (N-(3-oxododecanoyl)homoserine lactone); 0 (Toll-Like Receptors); 0 (Tumor Necrosis Factor-alpha); 6KA95X0IVO (Homoserine); OL659KIY4X (4-Butyrolactone)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170713
[Lr] Data última revisão:
170713
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170419
[St] Status:MEDLINE
[do] DOI:10.1111/apm.12690


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[PMID]:28373605
[Au] Autor:Amoh T; Murakami K; Kariyama R; Hori K; Irie Y; Viducic D; Hirota K; Igarashi J; Suga H; Kumon H; Miyake Y
[Ad] Endereço:Department of Oral Microbiology, Institute of Biomedical Sciences, Tokushima University Graduate School.
[Ti] Título:A Pseudomonas aeruginosa Quorum-Sensing autoinducer analog enhances the activity of antibiotics against resistant strains.
[So] Source:J Med Invest;64(1.2):101-109, 2017.
[Is] ISSN:1349-6867
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:In this study, we have investigated the effects of the newly synthesized analog of Pseudomonas aeruginosa quorum-sensing autoinducer named AIA-1 (autoinducer analog) against antibiotic-resistant bacteria. In vitro susceptibility and killing assays for P. aeruginosa PAO1ΔoprD mutant and clinical isolates were performed by using antibiotics and AIA-1. In an in vivo assay, a luminescent carbapenem-resistant strain derived from PAO1ΔoprD was injected into neutropenic ICR mice and bioluminescence images were acquired after the treatment with antibiotics and AIA-1. Additionally, we investigated the effects of the combination use against carbapenem-resistant Enterobacteriaceae (CRE). Using killing assays in P. aeruginosa, the survival rates in the presence of antibiotics and AIA-1 significantly decreased in comparison with those with antibiotics alone. Furthermore, dual treatment of biapenem and AIA-1 was more effective than biapenem alone in a mouse infection model. AIA-1 did not change the MICs in P. aeruginosa, suggesting that AIA-1 acts on the mechanism of antibiotic tolerance. Conversely, the MICs of antibiotics decreased in the presence of AIA-1 in some CRE strains, indicating that AIA-1 may require additional mechanism to act on CRE. In conclusion, AIA-1 may be a potent drug for clinical treatment of infections caused by antibiotic-resistant bacteria. J. Med. Invest. 64: 101-109, February, 2017.
[Mh] Termos MeSH primário: Antibacterianos/administração & dosagem
Homosserina/análogos & derivados
Lactonas/administração & dosagem
Pseudomonas aeruginosa/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Carbapenêmicos/farmacologia
Sinergismo Farmacológico
Homosserina/administração & dosagem
Homosserina/síntese química
Homosserina/química
Seres Humanos
Lactonas/síntese química
Lactonas/química
Camundongos
Camundongos Endogâmicos ICR
Infecções por Pseudomonas/tratamento farmacológico
Infecções por Pseudomonas/microbiologia
Pseudomonas aeruginosa/genética
Percepção de Quorum/efeitos dos fármacos
Tienamicinas/administração & dosagem
Resistência beta-Lactâmica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Carbapenems); 0 (Lactones); 0 (Thienamycins); 152833-54-0 (Pseudomonas aeruginosa autoinducer); 6KA95X0IVO (Homoserine); YR5U3L9ZH1 (biapenem)
[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:170405
[St] Status:MEDLINE
[do] DOI:10.2152/jmi.64.101



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