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Journal articles on the topic "Transporteurs ABC"

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Geillon, Flore, Doriane Trompier, Catherine Gondcaille, Gérard Lizard, and Stéphane Savary. "Transporteurs ABC peroxysomaux et adrénoleucodystrophie liée au chromosome X." médecine/sciences 28, no. 12 (December 2012): 1087–94. http://dx.doi.org/10.1051/medsci/20122812019.

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DAUCHY, S., N. TOURNIER, S. YOUSIF, A. JACOB, and X. DECLEVES. "Barrière hémato-encéphalique : implication des transporteurs ABC en neuropharmacologie." Réanimation 17, no. 7 (October 2008): 664–69. http://dx.doi.org/10.1016/j.reaurg.2008.07.013.

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Arnaud, L. "Systèmes de groupes sanguins : les transporteurs ABC rejoignent le club !" Transfusion Clinique et Biologique 20, no. 3 (June 2013): 280. http://dx.doi.org/10.1016/j.tracli.2013.04.096.

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ZHAO, Li-Xia, Cheng-Ji ZHOU, Arowu TANAKA, Masanori NAKATA, Takahiro HIRABAYASHI, Teruo AMACHI, Seiji SHIODA, Kazumitsu UEDA, and Nobuya INAGAKI. "Cloning, characterization and tissue distribution of the rat ATP-binding cassette (ABC) transporter ABC2/ABCA2." Biochemical Journal 350, no. 3 (September 8, 2000): 865–72. http://dx.doi.org/10.1042/bj3500865.

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The ABC1 (ABCA) subfamily of the ATP-binding cassette (ABC) transporter superfamily has a structural feature that distinguishes it from other ABC transporters. Here we report the cloning, molecular characterization and tissue distribution of ABC2/ABCA2, which belongs to the ABC1 subfamily. Rat ABC2 is a protein of 2434 amino acids that has 44.5%, 40.0% and 40.8% identity with mouse ABC1/ABCA1, human ABC3/ABCA3 and human ABCR/ABCA4 respectively. Immunoblot analysis showed that proteins of 260 and 250kDa were detected in COS-1 cells transfected with ABC2 having a haemagglutinin tag, while no band was detected in mock-transfected cells. After incubation with N-glycosidase F, the mobilities of the two proteins increased and a single band was detected, suggesting that ABC2 is a glycoprotein. Photoaffinity labelling with 8-azido-[α-32P]ATP confirmed that ATP binds to the ABC2 protein in the presence of Mg2+. RNA blot analysis showed that ABC2 mRNA is most abundant in rat brain. Examination of brain by in situ hybridization determined that ABC2 is expressed at high levels in the white matter, indicating that it is expressed in the oligodendrocytes. ABC2, therefore, is a glycosylated ABC transporter protein, and may play an especially important role in the brain. In addition, the N-terminal 60-amino-acid sequence of the human ABC1, which was missing from previous reports, has been determined.
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Mourez, M., M. Jéhanno, M. Hofnung, and E. Dassa. "Rôle, fonctionnement et structure des transporteurs à ATP binding cassette (ABC)." médecine/sciences 16, no. 3 (2000): 386. http://dx.doi.org/10.4267/10608/1658.

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Latif, Haythem, Merve Sahin, Janna Tarasova, Yekaterina Tarasova, Vasiliy A. Portnoy, Juan Nogales, and Karsten Zengler. "Adaptive Evolution of Thermotoga maritima Reveals Plasticity of the ABC Transporter Network." Applied and Environmental Microbiology 81, no. 16 (June 5, 2015): 5477–85. http://dx.doi.org/10.1128/aem.01365-15.

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ABSTRACTThermotoga maritimais a hyperthermophilic anaerobe that utilizes a vast network of ABC transporters to efficiently metabolize a variety of carbon sources to produce hydrogen. For unknown reasons, this organism does not metabolize glucose as readily as it does glucose di- and polysaccharides. The leading hypothesis implicates the thermolability of glucose at the physiological temperatures at whichT. maritimalives. After a 25-day laboratory evolution, phenotypes were observed with growth rates up to 1.4 times higher than and glucose utilization rates exceeding 50% those of the wild type. Genome resequencing revealed mutations in evolved cultures related to glucose-responsive ABC transporters. The native glucose ABC transporter, GluEFK, has more abundant transcripts either as a result of gene duplication-amplification or through mutations to the operator sequence regulating this operon. Conversely, BglEFGKL, a transporter of beta-glucosides, is substantially downregulated due to a nonsense mutation to the solute binding protein or due to a deletion of the upstream promoter. Analysis of the ABC2 uptake porter families for carbohydrate and peptide transport revealed that the solute binding protein, often among the transcripts detected at the highest levels, is predominantly downregulated in the evolved cultures, while the membrane-spanning domain and nucleotide binding components are less varied. Similar trends were observed in evolved strains grown on glycerol, a substrate that is not dependent on ABC transporters. Therefore, improved growth on glucose is achieved through mutations favoring GluEFK expression over BglEFGKL, and in lieu of carbon catabolite repression, the ABC transporter network is modulated to achieve improved growth fitness.
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Ogawa, Atsuko, Takashi Hashida-Okado, Masahiro Endo, Hirofumi Yoshioka, Takashi Tsuruo, Kazutoh Takesako, and Ikunoshin Kato. "Role of ABC Transporters in Aureobasidin A Resistance." Antimicrobial Agents and Chemotherapy 42, no. 4 (April 1, 1998): 755–61. http://dx.doi.org/10.1128/aac.42.4.755.

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ABSTRACT Aureobasidin A (AbA) has strong antifungal effects arising from an unusual mechanism. We show that AbA interacts with ATP-binding cassette (ABC) transporters in yeast and mammalian cells. We isolated a gene ofSaccharomyces cerevisiae that conferred resistance to AbA when the gene was present in multiple copies. The gene was identical toYOR1/YRS1, which confers resistance to oligomycin, reveromycin, and organic anions, none of which have structures similar to that of AbA. We also isolated an aur3 Rrecessive mutant of S. cerevisiae with increased resistance to AbA. Northern hybridization showed that theaur3 R mutant expressed not onlyYOR1 but also the ABC transporter-encoding genePDR5 at high levels. Genetic studies showed that theaur3 R mutant had a mutation in thePDR1 gene, which encodes a transcriptional regulator ofPDR5 and YOR1. Analysis of a yor1disruptant of the aur3/pdr1 mutant showed that both the functional YOR1 gene and the mutation in PDR1were necessary for AbA resistance. These results suggest thatYOR1 is more important than PDR5 for AbA resistance. We found in Candida albicans a novel gene whose sequence was similar to the sequence of YOR1 in S. cerevisiae. The amino acid sequence of the C. albicans YOR1 homolog showed no significant similarity to the sequences ofCDR1 and CDR2, which are ABC transporters ofC. albicans. Furthermore, AbA inhibited the efflux of the anticancer agent vincristine through P glycoproteins in cancer cells with multidrug resistance.
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Michaelis, Martin, Florian Rothweiler, Thomas Nerreter, Mohsen Sharifi, Taravat Ghafourian, and Jindrich Cinatl. "Karanjin interferes with ABCB1, ABCC1, and ABCG2." Journal of Pharmacy & Pharmaceutical Sciences 17, no. 1 (March 10, 2014): 92. http://dx.doi.org/10.18433/j3bw2s.

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PURPOSE: The prominent ATP-binding cassette (ABC) transporters ABCB1, ABCC1, and ABCG2 are involved in substance transport across physiological barriers and therefore in drug absorption, distribution, and elimination. They also mediate multi-drug resistance in cancer cells. Different flavonoids are known to interfere with different ABC transporters. Here, the effect of the furanoflavonol karanjin, a potential drug with antiglycaemic, gastroprotective, antifungal, and antibacterial effects, was investigated on ABCB1, ABCC1, and ABCG2-mediated drug transport in comparison to the flavonoids apigenin, genistein, and naringenin. METHODS: Cells expressing the relevant transporters (ABCB1: UKF-NB-3ABCB1, UKF-NB-3rVCR10; ABCC1: G62, PC-3rVCR20; ABCG2: UKF-NB-3ABCG2) were used in combination with specific fluorescent and cytotoxic ABC transporter substrates and ABC transporter inhibitors to study ABC transporter function. Moreover, the effects of the investigated flavonoids were determined on the ABC transporter ATPase activities. RESULTS: Karanjin interfered with drug efflux mediated by ABCB1, ABCC1, and ABCG2 and enhanced the ATPase activity of all three transporters. Moreover, karanjin exerted more pronounced effects than the control flavonoids apigenin, genistein, and naringenin on all three transporters. Most notably, karanjin interfered with ABCB1 at low concentrations being about 1µM. CONCLUSIONS: Taken together, these findings should be taken into account during further consideration of karanjin as a potential drug for different therapeutic indications. The effects on ABCB1, ABCC1, and ABCG2 may affect the pharmacokinetics of co-administered drugs. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.METHODS: Cells expressing the relevant transporters (ABCB1: UKF-NB-3ABCB1, UKF-NB-3rVCR10; ABCC1: G62, PC-3rVCR20; ABCG2: UKF-NB-3ABCG2) were used in combination with specific fluorescent and cytotoxic ABC transporter substrates and ABC transporter inhibitors to study ABC transporter function. Moreover, the effects of the investigated flavonoids were determined on the ABC transporter ATPase activities.RESULTS: Karanjin interfered with drug efflux mediated by ABCB1, ABCC1, and ABCG2 and enhanced the ATPase activity of all three transporters. Moreover, karanjin exerted more pronounced effects than the control flavonoids apigenin, genistein, and naringenin on all three transporters. Most notably, karanjin interfered with ABCB1 at low concentrations being about 1µM.CONCLUSIONS: Taken together, these findings should be taken into account during further consideration of karanjin as a potential drug for different therapeutic indications. The effects on ABCB1, ABCC1, and ABCG2 may affect the pharmacokinetics of co-administered drugs.
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Zhang, Wandong, Qing Yan Liu, Arsalan S. Haqqani, Ziying Liu, Caroline Sodja, Sonia Leclerc, Ewa Baumann, Christie E. Delaney, Eric Brunette, and Danica B. Stanimirovic. "Differential Expression of ABC Transporter Genes in Brain Vessels vs. Peripheral Tissues and Vessels from Human, Mouse and Rat." Pharmaceutics 15, no. 5 (May 22, 2023): 1563. http://dx.doi.org/10.3390/pharmaceutics15051563.

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Background: ATP-binding cassette (ABC) transporters comprise a superfamily of genes encoding membrane proteins with nucleotide-binding domains (NBD). These transporters, including drug efflux across the blood–brain barrier (BBB), carry a variety of substrates through plasma membranes against substrate gradients, fueled by hydrolyzing ATP. The expression patterns/enrichment of ABC transporter genes in brain microvessels compared to peripheral vessels and tissues are largely uncharacterized. Methods: In this study, the expression patterns of ABC transporter genes in brain microvessels, peripheral tissues (lung, liver and spleen) and lung vessels were investigated using RNA-seq and WesTM analyses in three species: human, mouse and rat. Results: The study demonstrated that ABC drug efflux transporter genes (including ABCB1, ABCG2, ABCC4 and ABCC5) were highly expressed in isolated brain microvessels in all three species studied; the expression of ABCB1, ABCG2, ABCC1, ABCC4 and ABCC5 was generally higher in rodent brain microvessels compared to those of humans. In contrast, ABCC2 and ABCC3 expression was low in brain microvessels, but high in rodent liver and lung vessels. Overall, most ABC transporters (with the exception of drug efflux transporters) were enriched in peripheral tissues compared to brain microvessels in humans, while in rodent species, additional ABC transporters were found to be enriched in brain microvessels. Conclusions: This study furthers the understanding of species similarities and differences in the expression patterns of ABC transporter genes; this is important for translational studies in drug development. In particular, CNS drug delivery and toxicity may vary among species depending on their unique profiles of ABC transporter expression in brain microvessels and BBB.
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Kropf, Christian, Karl Fent, Stephan Fischer, Ayako Casanova, and Helmut Segner. "ABC transporters in gills of rainbow trout (Oncorhynchus mykiss)." Journal of Experimental Biology 223, no. 15 (June 12, 2020): jeb221069. http://dx.doi.org/10.1242/jeb.221069.

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ABSTRACTFish gills are a structurally and functionally complex organ at the interface between the organism and the aquatic environment. Gill functions include the transfer of organic molecules, both natural ones and xenobiotic compounds. Whether the branchial exchange of organic molecules involves active transporters is currently not known. Here, we investigated the presence, diversity and functional activity of ATP-binding cassette (ABC) transporters in gills of juvenile rainbow trout. By means of RT-qPCR, gene transcripts of members from the abcb, abcc and abcg subfamilies were identified. Comparisons with mRNA profiles from trout liver and kidney revealed that ABC transporters known to have an apical localization in polarized epithelia, especially abcc2 and abcb1, were under-represented in the gills. In contrast, ABC transporters with mainly basolateral localization showed comparable gene transcript levels in the three organs. The most prominent ABC transporter in gills was an abcb subfamily member, which was annotated as abcb5 based on the synteny and phylogeny. Functional in vivo assays pointed to a role of branchial ABC transporters in branchial solute exchange. We further assessed the utility of primary gill cell cultures to characterize transporter-mediated branchial exchange of organic molecules, by examining ABC transporter gene transcript patterns and functional activity in primary cultures. The gill cultures displayed functional transport activity, but the ABC mRNA expression patterns were different to those of the intact gills. Overall, the findings of this study provide evidence for the presence of functional ABC transporter activity in gills of fish.
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Dissertations / Theses on the topic "Transporteurs ABC"

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Vorac, Jaroslav. "Le fonctionnement du transporteur ABC de Streptococcus pneumoniae impliqué dans la résistance contre les peptides antimicrobiens." Thesis, Université Grenoble Alpes (ComUE), 2016. http://www.theses.fr/2016GREAV009/document.

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Streptococcus pneumoniae, le pneumocoque, est un pathogène majeur causant plus d'un million de morts par an dans le monde. De plus en plus de souches de pneumocoques sont résistants aux antibiotiques, en faisant un problème majeur de santé publique dans le monde. Une partie des ces antibiotiques sont les peptides anti-microbiens (AMP), qui sont produit aussi bien par l'hôte que des bactéries pathogènes en tant que premier système de défense. On trouve dans le pneumocoque un transporteur ABC (ATP-Binding Cassette) lié à un système de deux composants (TCS) – la kinase d'histidine (HK) et le régulateur de réponse (RR), qui cible les AMP. Récemment, il a été démontré, que l'absence du transporteur ABC augmente la sensibilité à la bacitracine. Dans ce projet, nous avons essayé à comprendre le mécanisme fonctionnel entre le transporteur ABC et TCS en utilisant des outils in vivo et in vitro
Streptococcus pneumoniae, the pneumococcus, is a major human pathogen causing over a million deaths each year. Many pneumococcal strains display resistance towards antibiotics causing world-wide health concern. Some of these antibiotics are antimicrobial peptides (AMP), which are produced as a primary defense by hosts as well as pathogens. The pneumococcus harbors a system comprised of an ATP-binding cassette (ABC) transporter and a two-component system (TCS) composed of a histidine kinase (HK) and a response regulator (RR), which targets these molecules. It has been shown recently that the removal of this ABC transporter increases the sensitivity of the bacteria towards bacitracin. In this project, we tried to understand the functioning mechanism of the ABC transporter and the co-operation with the TCS using both in vivo and in vitro techniques
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Matar, Merheb Rachel Rima. "Caractérisation d’une nouvelle génération de détergents stabilisateurs des transporteurs abc en solution : cristallisation de BmrA, transporteur ABC bactérien." Thesis, Lyon 1, 2010. http://www.theses.fr/2010LYO10303.

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En raison de leur résistance aux agents chimiothérapeutiques, les transporteurs ABC de phénotype MDR ont attiré l'attention de la communauté scientifique. Notre projet vise à trouver des conditions dans lesquelles les transporteurs ABC restent fonctionnels en solution pour aboutir à la cristallisation de ces protéines dans une conformation active. Dans ce but, nous avons conçu et développé une nouvelle classe de détergents, à base de calix[4]arène, qui stabilisent ces protéines. Afin de résoudre la structure 3D à résolution atomique du transporteur ABC bactérien "BmrA", responsable de la résistance aux antibiotiques, nous avons utilisé une approche classique utilisant des détergents commerciaux en parallèle à nos détergents innovants. En présence de la Foscholine 12, nous avons obtenu des cristaux diffractant jusqu’à 5 Å de résolution. Cependant, les données de diffraction n’étaient pas suffisantes pour déterminer la structure tridimensionnelle complète de la protéine, seuls les domaines transmembranaires ont été résolus. D'autre part, nous avons atteint l'objectif de l'extraction, la purification et la stabilisation de ce transporteur à l'aide des détergents à base de calix [4] arène. Nous avons également montré que ces détergents promeuvent et améliorent la cinétique de cristallisation de BmrA, une étape que nous sommes en train d’optimiser, pour obtenir des cristaux de meilleure résolution, pour résoudre la structure 3D de BmrA qui sera utilisé pour concevoir des inhibiteurs adaptés
Due to their preponderance in the resistance to chemotherapies, the MDR ABC transporters have drawn the attention of the scientific community. Our project aimed at finding conditions in which ABC transporters are active in solution to lead the crystallization of these proteins in an active conformation. In this purpose, we conceived and developed a new class of detergents, based on calix[4]arene ring, that stabilize these proteins. In order to solve the 3D-structure to atomic resolution of bacterial ABC transporter “BmrA” responsible for antibiotic resistance, we used a classical approach with commercial detergents in addition to the innovative ones. We have crystallized the protein in presence of Foscholine 12 with a diffraction resolution up to 5 Å. The data was incomplete; solving partially the structure of the transmembrane domains. On the other hand, we have reached the objective of extraction, purification and stabilization of this transporter by using calix[4]arene-based detergents. We have also shown that these detergents promote and enhance the kinetics of crystallization of BmrA, a step that we are improving, to get crystals of better resolution, for resolving the BmrA 3D-structure which will be used to design adapted inhibitors
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Koraichi, Farah. "Étude in vivo / in vitro de l'effet de la zéaralénone sur l'expression de transporteurs ABC majeurs lors d'une exposition gestationnelle ou néonatale." Thesis, Lyon 1, 2012. http://www.theses.fr/2012LYO10314/document.

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La zéaralénone (ZEN) est une mycotoxine produite par des Fusarium qui contaminent les cultures céréalières. Oestrogéno-mimétique et perturbateur endocrinien, ses effets toxiques concernent l'appareil reproducteur. En amont de l'évaluation du risque lié à une exposition à de faibles doses de ZEN, nous nous sommes intéressés à l'effet de la ZEN sur le niveau d'expression de transporteurs ABC majeurs. Ces pompes d'efflux sont présentes dans les barrières de l'organisme (notamment les barrières testiculaires et placentaires) où elles jouent un rôle dans la protection des tissus contre la toxicité de leurs substrats xénobiotiques. Dans ce travail nous avons d'abord caractérisé le métabolisme et la distribution tissulaire de la ZEN chez le rat, puis avons évalué son effet respectivement à court et long terme sur l'expression des transporteurs ABC après une exposition gestationnelle et néonatale. Nos résultats mettent en évidence des différences de comportement toxicocinétique de la ZEN en fonction du genre et du statut hormonal, et une réelle exposition fœtale et néonatale via la mère. La ZEN module l'expression des transporteurs ABC majeurs in vivo (dans les organes maternels, le foie foetal, le testicule du jeune adulte exposé J1-J5). Les résultats obtenus sur modèles in vitro (lignées sertolienne et placentaire) suggèrent que ces modulations sont liées en partie à l'interaction de la ZEN avec les récepteurs aux oestrogènes. Les conséquences d'une modulation de l'expression des transporteurs ABC induite par la ZEN pourraient être dramatiques pour le développement et la santé des individus à l'âge adulte et doivent être évaluées
Zearalenone (ZEN) is a mycotoxin produced by Fusarium that infect cereal crops. This Estrogenmimetic and endocrine disruptor affects the reproductive system. Upstream of the risk assessment of exposure to low doses of ZEN, we are interested in the effect of ZEN on the expression level of major ABC transporters. These efflux pumps are present in the barriers of organism (including testicular and placental barriers), where they protect tissues against the toxicity of their xenobiotic substrates. In this work, we first characterized the metabolism and tissue distribution of ZEN in rat and then evaluated respectively its short and long-term effect on ABC transporters expression after gestational and neonatal exposure. Our results highlight differences in the toxicokinetic behavior of ZEN by gender and hormonal status, and fetal and neonatal real exposure via the mother. ZEN modulates the expression of major ABC transporters in vivo (in the maternal organs, fetal liver, testis of young adult exposed J1-J5). The results of in vitro models (sertoli and placental cell lines) suggest that these variations are partly due to the interaction of ZEN with the estrogen receptors. The consequences of expression modulations of ABC transporters induced by ZEN could be dramatic for the development and health of individuals in adulthood and should be evaluated
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Jorajuria, Sylvie. "Rôle des transporteurs ABC dans l'efficacité pharmacologique des antirétroviraux." Paris 5, 2003. http://www.theses.fr/2003PA05P618.

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L'échappement thérapeutique est un obstacle au traitement de l'infection par le VIH, qui repose notamment sur une modulation de la P-gp et des MRP. Dans le modèle de cultures primaires de macrophages humains, une induction transitoire de l'expression membranaire, de l'activité, et de l'expression des ARNm de la P-gp a été observée en réponse à l'infection. Elle est associée à une synthèse de TNF-a et pourrait résulter de l'interaction entre la gp120 virale et l'un des co-récepteurs du VIH i. E. CCR5. Le gène mrp4 suit le même profil d'expression alors que l'expression de mrp1 et mrp5 est induite au cours de la phase de réplication virale. Deux inhibiteurs de la P-gp et des MRP, le PSC833 et le probénécide, augmentent l'efficacité antivirale de l'AZT et de l'indinavir. Les voies de transduction induite par PSC833 pourrait expliquer l'augmentation d'expression de mrp4 et mrp5 par l'AZT et donc la meilleure efficacité de l'AZT
Treatment of AIDS is restricted by therapeutical escape, relying notably on modulation of P-gp and MRP. In primary cultures of human monocyte-derived macrophages, we evidence a transient increase of P-gp activity related to an increase of P-gp expression at cell surface and of P-gp mRNA. This transcriptional up-regulation is associated with a TNF-a overproduction and could result from the binding between viral gp120 and CCR5, one of HIV coreceptors. Same profile is obtained for MRP4 mRNA expression while those of MRP5 and MRP1 mRNA increase concomitantly with HIV replication. In parallel, we observe that anti-HIV effects of antiretroviral drugs such AZT and indinavir are increased when we inhibit the P-gp and/or MRP efflux with specific inhibitors (PSC833 and probenecid). Transduction pathways activated by PSC833 may account for AZT-induced mrp4 and mrp5 expression and thus for increased AZT antiviral efficacy in vitro
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Broccardo, Cyril. "Etude de la sous-classe ABCA de la famille des transporteurs ABC : Analyse génomique et inactivation fonctionnelle du gène ABC-1." Aix-Marseille 2, 2000. http://www.theses.fr/2000AIX22011.

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Mingam, Rozenn. "Etude de la modulation de la production et de l'action des cytokines cérébrales : le rôle du recepteur P2X7." Bordeaux 2, 2006. http://www.theses.fr/2006BOR21407.

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Fribourg, Pierre-Frédéric. "Analyse structurale de transporteurs membranaires ABC d'efflux par microscopie électronique." Paris 6, 2012. http://www.theses.fr/2012PA066579.

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Cette thèse a été consacré à l'analyse biochimique et structurale par microscopie électronique de 2 transporteurs membranaires « ATP-binding cassette » (ABC) BmrA de B. Subtilis et ABCC2, un transporteur humain. Les ABCs transporteurs sont responsables du transport ATP dépendant à travers les membranes cellulaires d'une large variété d’endo et de xénobiotiques organiques. Plusieurs ABC transporteurs, dont BmrA et ABCC2, sont responsables d’un phénotype de multirésistances cellulaire aux agents anticancéreux, antibiotiques ou antiviraux. La conception de nouveaux inhibiteurs est limitée par le faible niveau de connaissances structurales de ces transporteurs. Dans le cas de BmrA, l’originalité du travail a été d’obtenir la structure dans un environnement membranaire des conformations en absence et en présence de nucléotides. Pour cela, BmrA a été reconstitué à forte densité protéique dans une bicouche lipidique. Pour la forme apo, une reconstruction 3D à 23 Å de résolution a été obtenue par la technique de particule isolée en cryo-EM. Pour la forme post-hydrolytique, l'analyse de cristaux 2D a permis le calcul d'une carte de projection à 16 Å. L’ensemble des résultats permet d'établir formellement l'existence d'une forme ouverte apo-ATP vers le cytoplasme et d'une forme fermée ATP-lié ouverte vers le milieu extracellulaire favorisant un mécanisme de transport de drogues de type « soufflet ». Dans le cas d’ABCC2, le transporteur a été purifié et un modèle 3D à basse résolution d’une forme dimérique a été calculé. Les résultats ont mis en évidence une forme monomérique et une forme dimérique inédite d’ABCC2 démontrant sa capacité à former des organisations supramoléculaires
The goals of the PhD thesis is the biochemical and the structural analysis by cryo-electron microscopy of two « ATP-binding cassette » (ABC) membrane transporters, namely BmrA from B. Subtilis and ABCC2, a human transporter. ABC transporters are responsible for the ATP-dependent translocation across the cell membranes of a wide variety of organic endobiotics and xenobiotics. Several ABC transporters, including BmrA and ABCC2 are involved in a cellular multidrugs resistance against antibiotics, antiviral and anticancer agents. The absence of structural information on these ABC transporters prevents the conception of new inhibitors. In this context, we have characterized by electron microscopy BmrA in nucleotide-free and nucleotide bound conformation in a lipidic environment after reconstitution of BmrA at high protein densities. A tridimensional reconstruction at 23 Å resolution of the nucleotide-free conformation has been calculated from cryo-embebded samples by single particle analysis. A projection map at 16 Å of the nucleotide-bound conformation was calculated from 2D crystals. Overall, results revealed an inward-open conformation of BmrA in absence of nucleotides and an outward-facing conformation in post-hydrolytic state. This demonstrated a bellows-like mechanism of drugs transports involving a large conformational change that changes the cellular orientation of the drugs binding side upon ATP binding. ABCC2 has been purified and a 3D model at low resolution has been calculated from negatively stained images. Overall, the results have demonstrated the capacity of ABCC2 to be assembled in supramolecular organisation
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Lakli, Mounia. "Pharmacothérapie ciblée de variants d'ABCB4, le transporteur biliaire de phospholipides." Electronic Thesis or Diss., université Paris-Saclay, 2024. http://www.theses.fr/2024UPASQ026.

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ABCB4/MDR3 est une protéine transmembranaire qui assure la sécrétion de la phosphatidylcholine, un composant fondamental de la bile, au niveau de la membrane canaliculaire des hépatocytes. De nombreuses mutations qui touchent le gène encodant ce transporteur sont à l'origine de pathologies cholestatiques rares. La cholestase intrahépatique familiale progressive de type 3 (PFIC3) représente la forme la plus sévère de ces maladies. À ce jour, environ 50 % des patients ne répondent pas aux traitements conventionnels, faisant de la transplantation hépatique l'ultime alternative thérapeutique pour ces jeunes patients. Cette thèse a eu pour objectif d'identifier par une approche de criblage à haut débit, de nouveaux correcteurs pharmacologiques du trafic intracellulaire de trois variants d'ABCB4 (I541F, L556R et I490T), retenus dans le réticulum endoplasmique. Les résultats des analyses biochimiques et morphologiques nous ont permis de valider, dans nos modèles cellulaires, trois correcteurs de la maturation et de la localisation membranaire de deux variants. Néanmoins, à cause d'un effet inhibiteur de ces molécules sur la fonction d'ABCB4, un seul correcteur a pu restaurer de manière significative la fonction de ces deux variants. En association avec l'ivacaftor (VX 770, Kalydeco®), un modulateur d'activité approuvé pour la mucoviscidose, une amélioration et une potentialisation de l'activité a été obtenue. Dans le but d'explorer le mécanisme d'action de ses composés, des analyses de docking moléculaire in silico ont été réalisées et suggèrent une interaction des drogues avec les résidus d'ABCB4 impliqués dans la liaison/hydrolyse de l'ATP expliquant potentiellement l'effet inhibiteur de la fonction. De plus, in vitro, les molécules augmentent la stabilité à la membrane plasmique d'ABCB4-WT et semblent inhiber sa dégradation lysosomale. De façon intéressante, l'effet correcteur de ces molécules est conservé pour un autre variant intracellulaire du transporteur d'acides biliaires ABCB11. Cela permet d'envisager un traitement consensus des déficits des deux transporteurs ABC, ABCB4 et ABCB11. Pour conclure, nous avons identifié de nouveaux composés correcteurs pour les variants d'ABCB4 retenus au niveau intracellulaire. Ces résultats ouvrent la voie à leur optimisation chimique afin de fournir de nouveaux médicaments candidats comme alternative potentielle à la transplantation hépatique pour les patients atteints de formes sévères de maladies liées aux déficits d'ABCB4
ABCB4/MDR3 is a transmembrane protein that secretes phosphatidylcholine, a fundamental component of bile, to the canalicular membrane of hepatocytes. Numerous mutations in the gene encoding this transporter are responsible for rare cholestatic diseases, the most severe one being progressive familial intrahepatic cholestasis type 3 (PFIC3). To date, at least 50 % of patients do not respond to conventional treatments, making liver transplantation the ultimate alternative therapy. Thus, this thesis was dedicated to characterizing and validating new pharmacological correctors for three traffic-defective ABCB4 variants (I541F, L556R and I490T) retained in the endoplasmic reticulum. In cell models, the biochemical and morphological analyses allowed us to identify three molecules able to rescue the maturation and canalicular localization of two variants. However, due to an inhibitory effect of these molecules on ABCB4 function, only one corrector was able to significantly restore the function of these variants. Combined with ivacaftor (VX 770, Kalydeco®), an approved modulator of activity for cystic fibrosis, an improvement and potentiation of ABCB4 activity was obtained. In silico molecular docking analyses were carried out to explore the mechanism of action of these compounds, suggesting an interaction of the drugs with ABCB4 residues involved in ATP binding/hydrolysis, which could explain the function inhibition effect. Furthermore, in vitro, the newly identified molecules increase the plasma membrane stability of ABCB4-WT and appear to inhibit its lysosomal degradation. Interestingly, the corrective effect of these molecules is conserved for an intracellular variant of the bile acid transporter ABCB11. This suggests the prospect of a consensus treatment for deficiencies of both ABC transporters. In conclusion, we have identified novel corrector compounds for intracellularly-retained ABCB4 variants. These results pave the way for their optimization to provide new drug candidates as potential alternatives to liver transplantation for patients with severe forms of ABCB4-related diseases
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Ouellet, Mélissa. "La barrière hémato-encéphalique, les transporteurs ABC et la maladie d'Alzheimer." Thesis, Université Laval, 2008. http://www.theses.ulaval.ca/2008/25310/25310.pdf.

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Schmid, Aline. "ABC transporteurs de Toxoplasma gondii et résistance médicamenteuse. Caractérisation et approche de la fonctionnalité dans les souches de référence, cliniques et traitées expérimentalement par la sulfadiazine." Reims, 2008. http://www.theses.fr/2008REIMM207.

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La @toxoplasmose est une zoonose due à un parasite intracellulaire obligatoire, Toxoplasma gondii. Les traitements de la toxoplasmose reposent sur un nombre limité de molécules. Outre la présence de mutations et/ou la surexpression sur les gènes DHFR et DHPS, l’implication de protéines de transport, telles que les Pgp et/ou les MRP pourrait intervenir dans les échecs. Notre étude a porté sur les ABC transporteurs membranaires entiers, appartenant aux familles ABC. B (TgABC. B1 et TgABC. B2) et ABC. C (TgABC. C1). Sur les souches de référence représentatives des types I, II et III, nous avons montré que les gènes codant pour les ABC transporteurs sont plus exprimés sur la souche RH. De plus, nous avons mis en évidence une expression plus importante pour TgABC. B1 (au niveau transcriptionnel et traductionnel) que pour les deux autres ABC transporteurs sur les souches représentatives des trois génotypes. L’existence de Pgp fonctionnelles chez T. Gondii est montrée avec une activité d’efflux identique pour les trois génotypes. Nous nous sommes ensuite attachés à rechercher les mécanismes de résistance sur trois souches résistantes à la sulfadiazine. Nous avons montré des variations des niveaux d’expression des ABC transporteurs qui paraissent liées au génotype de la souche plutôt qu’à son niveau de sensibilité à la sulfadiazine. Nous avons surtout montré une augmentation de l’activité d’efflux due aux Pgp, dans les souches résistantes. Nous nous sommes également intéressés à l’influence d’un traitement prolongé in utero par pyriméthamine/sulfadoxine sur une souche responsable de toxoplasmose congénitale. Nous avons observé une augmentation des transcrits de TgABC. B1 et TgABC. C1 après traitement médicamenteux associée à une augmentation de l’activité d’efflux des Pgp, indiquant une modification phénotypique de la souche sous l’influence d’un traitement antitoxoplasmique. Nous avons obtenu par pression médicamenteuse à des doses croissantes une souche RH résistante à la sulfadiazine. Cette évolution ne s’accompagne pas d’une modulation des transcrits des gènes analysés, mais de l’individualisation d’une population présentant une augmentation de la vitesse d’efflux des Pgp
The @apicomplexan Toxoplasma gondii, an obligate intracellular parasite, can infect humans and a wide range of vertebrates leading to toxoplasmosis. Treatment of toxoplasmosis usually uses a combination of a sulfamide with pyrimethamine; however, several failures have been reported in spite of a good observance of treatments. Common mechanisms of resistance are variations on the genes sequence encoding to the drug target (DHFR, DHPS) and/or on ABC (ATP Binding Cassette) with Pgp and MRP genes. In order to understand the failure mechanisms in T. Gondii, the objective of this study is to analyse full membrane ABC transporters TgABC. B1 and TgABC. B2: Pgp, TgABC. C1: MRP. The population structure of T. Gondii consists of three principal clonal lineages (types I,II and III) correlated with virulence expression. The three ABC genes are constitutively expressed in the three major T. Gondii genotypes but TgABC. B1 demonstrated a higher expression in virulent type I, at both transcriptional and translational levels. The existence of functional Pgp at T. Gondii is shown with an activity of efflux identical for three genotypes. A recent study on the strain’s sensitivity to treatment identify three strains with a weak sensitivity to sulfadiazine. The study of expression levels of three ABC genes didn’t show significant variation between resistant and sensitive strains. We showed an increase of the efflux activity to Pgp for the resistant strains. We were also interested in the influence of a treatment in utero by pyriméthamine/sulfadoxine on a congenital toxoplasmosis strain. We observed an increase of expression levels of TgABC. B1 and TgABC. C1 after treatment associated with an increase of the efflux activity of the Pgp, implying a modification phénotypic of the strain after toxoplasmosis treatment. We obtained by pressure in increasing doses a resistant RH strain for the sulfadiazine. This result doesn’t come along with a modulation of expression levels on the analysis genes, but with the population individualization which increase of the Pgp efflux activity
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Books on the topic "Transporteurs ABC"

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Geisler, Markus, ed. Plant ABC Transporters. Cham: Springer International Publishing, 2014. http://dx.doi.org/10.1007/978-3-319-06511-3.

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Procko, Erik. General mechanisms for ABC transporters revealed by the transporter associated with antigen processing. Cambridge, Mass: Harvard University, 2008.

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Boumendjel, Ahcne, Jean Boutonnat, and Jacques Robert, eds. ABC Transporters and Multidrug Resistance. Hoboken, NJ, USA: John Wiley & Sons, Inc., 2009. http://dx.doi.org/10.1002/9780470495131.

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George, Anthony M., ed. ABC Transporters - 40 Years on. Cham: Springer International Publishing, 2016. http://dx.doi.org/10.1007/978-3-319-23476-2.

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Ahcène, Boumendjel, Boutonnat Jean, and Robert Jacques M. D, eds. ABC transporters and multidrug resistance. Hoboken, N.J: John Wiley & Sons, 2009.

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B, Holland I., ed. ABC proteins: From bacteria to man. Amsterdam: Academic Press, 2003.

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Efferth, Thomas, ed. Resistance to Targeted ABC Transporters in Cancer. Cham: Springer International Publishing, 2015. http://dx.doi.org/10.1007/978-3-319-09801-2.

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Ponte-Sucre, Alicia. ABC transporters in microorganisms: Research, innovation and value as targets against drug resistance. Norfolk, UK: Caister Academic, 2009.

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Geisler, Markus. Plant ABC Transporters. Springer, 2016.

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Geisler, Markus. Plant ABC Transporters. Springer, 2014.

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Book chapters on the topic "Transporteurs ABC"

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Lage, Hermann. "ABC-Transporters." In Encyclopedia of Cancer, 1–5. Berlin, Heidelberg: Springer Berlin Heidelberg, 2014. http://dx.doi.org/10.1007/978-3-642-27841-9_13-5.

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Scherrmann, Jean-Michel, Kim Wolff, Christine A. Franco, Marc N. Potenza, Tayfun Uzbay, Lisiane Bizarro, David C. S. Roberts, et al. "ABC Transporters." In Encyclopedia of Psychopharmacology, 1. Berlin, Heidelberg: Springer Berlin Heidelberg, 2010. http://dx.doi.org/10.1007/978-3-540-68706-1_1099.

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Bates, Susan E., and Tito Fojo. "ABC Transporters." In Handbook of Anticancer Pharmacokinetics and Pharmacodynamics, 267–88. Totowa, NJ: Humana Press, 2004. http://dx.doi.org/10.1007/978-1-59259-734-5_17.

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Lage, Hermann. "ABC-Transporters." In Encyclopedia of Cancer, 17–21. Berlin, Heidelberg: Springer Berlin Heidelberg, 2014. http://dx.doi.org/10.1007/978-3-662-46875-3_13.

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Lage, Hermann. "ABC-Transporters." In Encyclopedia of Cancer, 10–13. Berlin, Heidelberg: Springer Berlin Heidelberg, 2011. http://dx.doi.org/10.1007/978-3-642-16483-5_13.

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Grube, Markus, and Gabriele Jedlitschky. "ABC Transporters." In Encyclopedia of Molecular Pharmacology, 1–7. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-21573-6_174-1.

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Grube, Markus, and Gabriele Jedlitschky. "ABC Transporters." In Encyclopedia of Molecular Pharmacology, 1–7. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-57401-7_174.

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Lackner, K. J., and D. Peetz. "ABC-Transporter." In Springer Reference Medizin, 3–4. Berlin, Heidelberg: Springer Berlin Heidelberg, 2019. http://dx.doi.org/10.1007/978-3-662-48986-4_59.

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Lackner, K. J., and D. Peetz. "ABC-Transporter." In Lexikon der Medizinischen Laboratoriumsdiagnostik, 1. Berlin, Heidelberg: Springer Berlin Heidelberg, 2018. http://dx.doi.org/10.1007/978-3-662-49054-9_59-1.

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Xu, YanXia, and YanHua Qi. "Monocot ABC Transporters." In Signaling and Communication in Plants, 203–17. Cham: Springer International Publishing, 2014. http://dx.doi.org/10.1007/978-3-319-06511-3_11.

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Conference papers on the topic "Transporteurs ABC"

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LOCHER, KASPAR. "STRUCTURES AND REACTION MECHANISMS OF ABC TRANSPORTERS." In 23rd International Solvay Conference on Chemistry. WORLD SCIENTIFIC, 2014. http://dx.doi.org/10.1142/9789814603836_0030.

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Ettouati, Laurent, Marie-Emmanuelle Million, Ophélie Arnaud, Géraldine Agusti, Waël Zeinyeh, Lucia Gonzalez-Lobato, Ali Koubeissi, et al. "Advances in peptidomimetics as inhibitors of ABC transporters." In 1st International Electronic Conference on Medicinal Chemistry. Basel, Switzerland: MDPI, 2015. http://dx.doi.org/10.3390/ecmc-1-a043.

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Pecks, U., L. Schmieding, Y. Sawierucha, K. Lüchow, N. Maass, and W. Rath. "LXR und ABC-Transporter-Expression im Trophoblast bei IUGR." In 62. Kongress der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe – DGGG'18. Georg Thieme Verlag KG, 2018. http://dx.doi.org/10.1055/s-0038-1671434.

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Schmieding, L., Y. Sawierucha, K. Lüchow, L. Segger, N. Maass, W. Rath, and U. Pecks. "LXR und ABC-Transporter-Expression im Trophoblast bei IUGR." In 28. Deutscher Kongress für Perinatale Medizin. Georg Thieme Verlag KG, 2017. http://dx.doi.org/10.1055/s-0037-1607686.

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Huynh, Tony, Amanda Tivnan, Marcia Munoz, Leanna Cheung, Anasuya Vishvanath, Claudia Flemming, Fujiko Watt, et al. "Abstract 1834: Targeting ABC transporters in cancer through small molecule inhibitors." In Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL. American Association for Cancer Research, 2012. http://dx.doi.org/10.1158/1538-7445.am2012-1834.

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Matsui, Hirofumi, and Hiromi Kurokawa. "Abstract 1285A: Erythropoietin can cancelchemo-resistances viadown regulation of ABC transporters." In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.sabcs18-1285a.

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Matsui, Hirofumi, and Hiromi Kurokawa. "Abstract 1285A: Erythropoietin can cancelchemo-resistances viadown regulation of ABC transporters." In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.am2019-1285a.

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KELLY, LIBUSHA, RACHEL KARCHIN, and ANDREJ SALI. "PROTEIN INTERACTIONS AND DISEASE PHENOTYPES IN THE ABC TRANSPORTER SUPERFAMILY." In Proceedings of the Pacific Symposium. WORLD SCIENTIFIC, 2006. http://dx.doi.org/10.1142/9789812772435_0006.

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Durmus, Selvi, M. A. van der Valk, S. F. Teunissen, Els Wagenaar, Jos Beijnen, and Alfred H. Schinkel. "Abstract 4419: The role of ABC transporters in PhIP-induced colon carcinogenesis." In Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL. American Association for Cancer Research, 2012. http://dx.doi.org/10.1158/1538-7445.am2012-4419.

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Piontek, M., L. Quell, and F. Grebien. "ABC transporters modulate the response of AML cells to Menin-MLL inhibitors." In 35. Jahrestagung der Kind-Philipp-Stiftung für pädiatrisch onkologische Forschung. Georg Thieme Verlag KG, 2024. http://dx.doi.org/10.1055/s-0044-1786608.

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Reports on the topic "Transporteurs ABC"

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Pasinelli, Piera, and Dena Jacob. Rethinking Drug Treatment Approaches in ALS by Targeting ABC Efflux Transporters. Fort Belvoir, VA: Defense Technical Information Center, December 2014. http://dx.doi.org/10.21236/ada615391.

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Jenness, Mark, and Angus Murphy. Analysis of plant ABCB organic acid transporters (Final Report). Office of Scientific and Technical Information (OSTI), November 2020. http://dx.doi.org/10.2172/1719140.

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Yedidia, I., H. Senderowitz, and A. O. Charkowski. Small molecule cocktails designed to impair virulence targets in soft rot Erwinias. Israel: United States-Israel Binational Agricultural Research and Development Fund, 2020. http://dx.doi.org/10.32747/2020.8134165.bard.

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Chemical signaling between beneficial or pathogenic bacteria and plants is a central factor in determining the outcome of plant-microbe interactions. Pectobacterium and Dickeya (soft rot Erwinias) are the major cause of soft rot, stem rot, and blackleg formed on potato and ornamentals, currently with no effective control. Our major aim was to establish and study specific bacterial genes/proteins as targets for anti-virulence compounds, by combining drug design tools and bioinformatics with experimental work. The approach allowed us to identify and test compounds (small molecules) that specifically interfere with the activities of these targets, by this impairing bacterial virulence. Two main targets were selected within the frame of the BARD project. The first is the ATP-binding cassette (ABC) transporters and methyl-accepting chemotaxis proteins (MCP) that have been characterized here for the first time in Pectobacteriaceae, and the second is the quorum sensing (QS) machinery of Pectobacterium with its major proteins and in particular, the AHL synthase ExpI that was identified as the preferred target for inhibition. Both systems are strongly associated with bacterial virulence and survival in planta. We found that Pectobacteriaceae, namely Dickeya and Pectobacterium, encode more ABC transporters and MCP in their genomes, compared to other bacteria in the order. For MCP, soft rot Pectobacteriaceae not only contain more than 30 MCP genes per strain, but also have more diverse ligand binding domains than other species in the Enterobacteriales. These findings suggest that both ABC transporters and MCP are important for soft rot Pectobacteriaceae pathogenicity. We now have a selection of mutants in these proteins that may be further explored to understand their direct involvement in virulence. In parallel, we studied the QS central proteins in pectobacteria, the signaling molecule N-acyl-homoserine lactone synthase, ExpI, and the response regulator ExpR, and established their phylogenetic relations within plant pathogenic Gram negative bacteria. Next, these proteins were used for virtual screening of millions of compounds in order to discover new compounds with potential to interfere with the QS machinery. Several natural compounds were tested for their interference with virulence related traits in Pectobacterium and their capability to minimize soft rot infections. Our findings using microcalorimetric binding studies have established for the first time direct interaction between the protein ExpI and two natural ligands, the plant hormone salicylic acid and the volatile compound carvacrol. These results supported a model by which plants interfere with bacterial communication through interkingdom signaling. The collaborative project yielded two research papers and a comprehensive review, which included new computational and bioinformatics data, in Annu. Rev. Phytopathol., the highest ranked journal in phytopathology. Additional two papers are in preparation. In order to transform the fundamental knowledge that have been gained during this collaborative BARD project into agricultural practice, to control soft rot bacteria, we have submitted a continual project.
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Shani, Uri, Lynn Dudley, Alon Ben-Gal, Menachem Moshelion, and Yajun Wu. Root Conductance, Root-soil Interface Water Potential, Water and Ion Channel Function, and Tissue Expression Profile as Affected by Environmental Conditions. United States Department of Agriculture, October 2007. http://dx.doi.org/10.32747/2007.7592119.bard.

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Constraints on water resources and the environment necessitate more efficient use of water. The key to efficient management is an understanding of the physical and physiological processes occurring in the soil-root hydraulic continuum.While both soil and plant leaf water potentials are well understood, modeled and measured, the root-soil interface where actual uptake processes occur has not been sufficiently studied. The water potential at the root-soil interface (yᵣₒₒₜ), determined by environmental conditions and by soil and plant hydraulic properties, serves as a boundary value in soil and plant uptake equations. In this work, we propose to 1) refine and implement a method for measuring yᵣₒₒₜ; 2) measure yᵣₒₒₜ, water uptake and root hydraulic conductivity for wild type tomato and Arabidopsis under varied q, K⁺, Na⁺ and Cl⁻ levels in the root zone; 3) verify the role of MIPs and ion channels response to q, K⁺ and Na⁺ levels in Arabidopsis and tomato; 4) study the relationships between yᵣₒₒₜ and root hydraulic conductivity for various crops representing important botanical and agricultural species, under conditions of varying soil types, water contents and salinity; and 5) integrate the above to water uptake term(s) to be implemented in models. We have made significant progress toward establishing the efficacy of the emittensiometer and on the molecular biology studies. We have added an additional method for measuring ψᵣₒₒₜ. High-frequency water application through the water source while the plant emerges and becomes established encourages roots to develop towards and into the water source itself. The yᵣₒₒₜ and yₛₒᵢₗ values reflected wetting and drying processes in the rhizosphere and in the bulk soil. Thus, yᵣₒₒₜ can be manipulated by changing irrigation level and frequency. An important and surprising finding resulting from the current research is the obtained yᵣₒₒₜ value. The yᵣₒₒₜ measured using the three different methods: emittensiometer, micro-tensiometer and MRI imaging in both sunflower, tomato and corn plants fell in the same range and were higher by one to three orders of magnitude from the values of -600 to -15,000 cm suggested in the literature. We have added additional information on the regulation of aquaporins and transporters at the transcript and protein levels, particularly under stress. Our preliminary results show that overexpression of one aquaporin gene in tomato dramatically increases its transpiration level (unpublished results). Based on this information, we started screening mutants for other aquaporin genes. During the feasibility testing year, we identified homozygous mutants for eight aquaporin genes, including six mutants for five of the PIP2 genes. Including the homozygous mutants directly available at the ABRC seed stock center, we now have mutants for 11 of the 19 aquaporin genes of interest. Currently, we are screening mutants for other aquaporin genes and ion transporter genes. Understanding plant water uptake under stress is essential for the further advancement of molecular plant stress tolerance work as well as for efficient use of water in agriculture. Virtually all of Israel’s agriculture and about 40% of US agriculture is made possible by irrigation. Both countries face increasing risk of water shortages as urban requirements grow. Both countries will have to find methods of protecting the soil resource while conserving water resources—goals that appear to be in direct conflict. The climate-plant-soil-water system is nonlinear with many feedback mechanisms. Conceptual plant uptake and growth models and mechanism-based computer-simulation models will be valuable tools in developing irrigation regimes and methods that maximize the efficiency of agricultural water. This proposal will contribute to the development of these models by providing critical information on water extraction by the plant that will result in improved predictions of both water requirements and crop yields. Plant water use and plant response to environmental conditions cannot possibly be understood by using the tools and language of a single scientific discipline. This proposal links the disciplines of soil physics and soil physical chemistry with plant physiology and molecular biology in order to correctly treat and understand the soil-plant interface in terms of integrated comprehension. Results from the project will contribute to a mechanistic understanding of the SPAC and will inspire continued multidisciplinary research.
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