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Pompes à efflux et virulence chez Pseudomonas aeruginosa, une interconnexion ? : Étude de l'impact du profil d'expression des pompes à efflux sur le système de sécrétion de type III et sur le quorum sensing chez Pseudomonas aeruginosa
Authors: --- ---
Year: 2014 Publisher: Bruxelles: UCL. Faculté de pharmacie et des sciences biomédicales,

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Abstract

Pseudomonas aeruginosa is an opportunistic bacterium which causes many nosocomial infections and increases morbidity and mortality in infected patients. This gram-negative bacterium has several virulence mechanisms, like the type III secretion system (T3SS), and uses quorum sensing as interbacterial communication ; this system controls the transcription of multiple genes, including genes coding for virulence factors (pyocyanin and elastase for instance). P. aeruginosa also possesses many antibiotic resistance mechanisms, including active efflux. These efflux pumps can export the autoinducers of quorum sensing, and therefore have an impact on pathogenicity of P. aeruginosa.In this work, we were interested in the interactions between three systems (efflux pumps, T3SS and quorum sensing), more specifically, in the effect that modification of pumps expression may have on T3SS and quorum sensing. Current literature on this topic presents only fragmental data, with papers examining only two systems together and, when they examine efflux, considering only one pump and its impact on virulence. For this purpose, we use the reference strain PAO1 and mutants thereof which overexpress one pump ore are deleted for the genes of one pump, namely MexAB-OprM, MexCD-OprJ, MexEF-OprN and MexXy –OprM.According to our results, the pumps expression profile seems to have an impact on some virulence parameters. We showed an increased production of pyocyanin in strains deficient for the expression of one pump or the presence of a pharmacological inhibitor of efflux. As autoinducers can be exported by efflux pumps, we suggest that their inactivation causes the accumulation of autoinducers which in its turn activates quorum sensing. We did not see any effect on elastase production, which may suggest that other regulations than quorum sensing are involved in the elastase production. In general, we did not observe any impact of pump expression profile on T3SS, but we did not investigate all genes of T3SS neither genes involved in its regulation. Many mechanisms and regulations are still to examine in order to understand the connections between efflux and virulence. Thus, understanding these mechanisms and links between them may help proposing research strategies to evaluate new therapies against resistance and /or pathogenicity of Pseudomonas aeruginosa. Pseudomonas aeruginosa est une bactérie opportuniste, provoquant de nombreuses infections nosocomiales et augmentant la morbidité et la mortalité chez les patients infectés. Cette bactérie à Gram négatif possède de nombreux mécanismes de virulence, tels que le système de sécrétion de type III(T3SS), et utilise le quorum sensing comme communication inter-bactér ienne ; ce système contrôle la transcription de nombreux gènes, dont ceux de la virulence (pyocyanine et élastase notamment). P. aeruginosa possède également de nombreux mécanismes de résistance aux antibiotiques, notamment l'expression de pompes à efflux au niveau de sa membrane. Ces pompes peuvent effluer les autoinducteurs du quorum sensing, et par conséquent avoir un effet sur la pathogénicité de Paeruginosa.Dans le cadre de. ce mémoire, nous nous sommes intéressés à l'interconnexion des trois systèmes (pompes à efflux, T3SS et quorum sensing), en particulier à l'effet que la modification de l'expression des pompes à efflux peut avoir sur le T3SS et le quorum sensing dans une même souche bactérienne. En effet, dans la littérature, les auteurs n'étudiaient que deux systèmes à la fois et, lorsqu'ils étudiaient l'efflux, ils n'étudiaient l'effet que d'une seule pompe sur la virulence. Dans ce but, nous avons utilisé des souches dérivant toutes de la souche de référence PA01 et montrant soit une surexpress ion d'une des pompes soit une délétion des gènes d'une des pompes, et ce, pour chacune des quatre pompes à efflux étudiées (MexAB-OprM, MexCD-OprJ, MexEF-OprN et MexXY-OprM) .Nous avons montré que le profil d'expression des pompes semble avoir un impact sur certains paramètres de virulence, car nous avons observé une production accrue de pyocyanine dans les souches déficientes pour un système d'efflux ou en présence d'inhibiteur pharmacologique de l'efflux. Comme les autoinducteurs peuvent être substrats des pompes, nous suggérons que ces molécules peuvent s'accumuler dans le cytoplasme bactérien et activer le quorum sensing lorsque l'efflux est inactivé. Nous n'avons par contre pas observé d'effet sur la production d'élastase ; il est possible que d'autres régulations que le quorum sensing interviennent dans la production de cette enzyme. Nous n'avons pas observé, en général, d'effet du profil d'expression des pompes sur le T3SS, mais nous n'avons pas étudié tous les gènes codant pour celui-ci, ni ceux de sa régulation. De nombreux mécanismes et régulations sont encore à étudier afin de comprendre les interconnexions entre efflux et virulence.Enfin, comprendre ces mécanismes et les relations qui existent entre eux permettrait d'entreprendre des études de recherche de thérapies contre la résistance et/ou la pathogénicité de Pseudomonas aeruginosa.

G protein pathways.
Authors: ---
ISBN: 1281011223 9786611011222 0080496938 012182246X Year: 2002 Publisher: San Diego ; London : Academic Press,

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Abstract

This third volume in the trio covering G proteins, features integrated approaches to studying G proteins. Methods pertaining to signaling mechanisms are presented, including theoretical and modeling approaches, biochemistry and molecular biology, and cell biology and physiology. The techniques for studying the structure and function of G proteins are important not only to those with specific research interests in them, but also endocrinologists and pharmacologists conducting research on signaling mechanisms that are increasingly understood to interact with G proteins.

Keywords

Cell adhesion molecules. --- Cell receptors. --- G proteins. --- Membrane Glycoproteins --- Biochemical Processes --- Membrane Transport Proteins --- Enzymes and Coenzymes --- Cell Physiological Processes --- Carrier Proteins --- GTP Phosphohydrolases --- Intracellular Signaling Peptides and Proteins --- Membrane Proteins --- Cell Physiological Phenomena --- Proteins --- Biochemical Phenomena --- Chemicals and Drugs --- Peptides --- Chemical Processes --- Acid Anhydride Hydrolases --- Amino Acids, Peptides, and Proteins --- Chemical Phenomena --- Phenomena and Processes --- Hydrolases --- GTP-Binding Proteins --- Heterotrimeric GTP-Binding Proteins --- Ion Channels --- Enzymes --- Signal Transduction --- Human Anatomy & Physiology --- Health & Biological Sciences --- Animal Biochemistry --- Receptor Mediated Signal Transduction --- Signal Transduction Pathways --- Signal Transduction Systems --- Receptor-Mediated Signal Transduction --- Signal Pathways --- Pathway, Signal --- Pathway, Signal Transduction --- Pathways, Signal --- Pathways, Signal Transduction --- Receptor-Mediated Signal Transductions --- Signal Pathway --- Signal Transduction Pathway --- Signal Transduction System --- Signal Transduction, Receptor-Mediated --- Signal Transductions --- Signal Transductions, Receptor-Mediated --- System, Signal Transduction --- Systems, Signal Transduction --- Transduction, Signal --- Transductions, Signal --- Biocatalysts --- Ion Channel --- Ionic Channel --- Ionic Channels --- Membrane Channel --- Membrane Channels --- Channel, Ion --- Channel, Ionic --- Channel, Membrane --- Channels, Ion --- Channels, Ionic --- Channels, Membrane --- Heterotrimeric G-Proteins --- G-Proteins, Heterotrimeric --- GTP-Binding Proteins, Heterotrimeric --- Heterotrimeric G Proteins --- Heterotrimeric GTP Binding Proteins --- G-Protein --- GTP-Binding Protein --- GTP-Regulatory Protein --- Guanine Nucleotide Coupling Protein --- G-Proteins --- GTP-Regulatory Proteins --- Guanine Nucleotide Regulatory Proteins --- G Protein --- G Proteins --- GTP Binding Protein --- GTP Binding Proteins --- GTP Regulatory Protein --- GTP Regulatory Proteins --- Protein, GTP-Binding --- Protein, GTP-Regulatory --- Proteins, GTP-Binding --- Proteins, GTP-Regulatory --- Chemical Phenomenon --- Chemical Process --- Physical Chemistry Phenomena --- Physical Chemistry Process --- Physicochemical Phenomenon --- Physicochemical Process --- Chemical Concepts --- Physical Chemistry Concepts --- Physical Chemistry Processes --- Physicochemical Concepts --- Physicochemical Phenomena --- Physicochemical Processes --- Chemical Concept --- Chemistry Process, Physical --- Chemistry Processes, Physical --- Concept, Chemical --- Concept, Physical Chemistry --- Concept, Physicochemical --- Concepts, Chemical --- Concepts, Physical Chemistry --- Concepts, Physicochemical --- Phenomena, Chemical --- Phenomena, Physical Chemistry --- Phenomena, Physicochemical --- Phenomenon, Chemical --- Phenomenon, Physicochemical --- Physical Chemistry Concept --- Physicochemical Concept --- Process, Chemical --- Process, Physical Chemistry --- Process, Physicochemical --- Processes, Chemical --- Processes, Physical Chemistry --- Processes, Physicochemical --- Polypeptides --- Biochemical Concepts --- Biochemical Phenomenon --- Biochemical Process --- Phenomena, Biochemical --- Biochemical Concept --- Concept, Biochemical --- Concepts, Biochemical --- Phenomenon, Biochemical --- Process, Biochemical --- Processes, Biochemical --- Gene Products, Protein --- Gene Proteins --- Protein Gene Products --- Proteins, Gene --- Cell Physiological Phenomenon --- Cell Physiological Process --- Physiology, Cell --- Cell Physiology --- Phenomena, Cell Physiological --- Phenomenon, Cell Physiological --- Physiological Process, Cell --- Physiological Processes, Cell --- Process, Cell Physiological --- Processes, Cell Physiological --- Cells --- Integral Membrane Protein --- Membrane Protein --- Membrane-Associated Proteins --- Cell Membrane Proteins --- Cell Surface Proteins --- Integral Membrane Proteins --- Surface Proteins --- Membrane Associated Proteins --- Membrane Protein, Integral --- Membrane Proteins, Integral --- Protein, Integral Membrane --- Protein, Membrane --- Proteins, Cell Membrane --- Proteins, Cell Surface --- Proteins, Integral Membrane --- Proteins, Membrane --- Proteins, Membrane-Associated --- Proteins, Surface --- Intracellular Signaling Peptides --- Intracellular Signaling Proteins --- Peptides, Intracellular Signaling --- Proteins, Intracellular Signaling --- Signaling Peptides, Intracellular --- Signaling Proteins, Intracellular --- GTP Phosphohydrolase --- GTPase --- GTPases --- Guanosine Triphosphate Phosphohydrolases --- Guanosinetriphosphatases --- Phosphohydrolase, GTP --- Phosphohydrolases, GTP --- Phosphohydrolases, Guanosine Triphosphate --- Triphosphate Phosphohydrolases, Guanosine --- Binding Protein --- Binding Proteins --- Transport Proteins --- Protein, Binding --- Proteins, Binding --- Proteins, Carrier --- Proteins, Transport --- Coenzymes and Enzymes --- Cell Surface Glycoprotein --- Membrane Glycoprotein --- Surface Glycoprotein --- Cell Surface Glycoproteins --- Surface Glycoproteins --- Glycoprotein, Cell Surface --- Glycoprotein, Membrane --- Glycoprotein, Surface --- Glycoproteins, Cell Surface --- Glycoproteins, Membrane --- Glycoproteins, Surface --- Surface Glycoprotein, Cell --- Surface Glycoproteins, Cell --- Biological Pumps --- Metabolic Pumps --- Permeases --- Pump, Biologic --- Pump, Biological --- Pump, Metabolic --- Pumps, Biological --- Pumps, Metabolic --- Biological Pump --- Membrane Transporters --- Metabolic Pump --- Biologic Pump --- Transport Proteins, Membrane --- Transporters, Membrane --- physiology --- Anhydride Hydrolases, Acid --- Hydrolases, Acid Anhydride --- Cell Signaling --- Cell Communication --- Receptor-CD3 Complex, Antigen, T-Cell --- Receptor Cross-Talk --- Feedback, Physiological --- Gasotransmitters --- Molecular Mechanisms of Pharmacological Action --- Molecular Biology --- Cell Membrane --- Membranes --- Protein Binding --- Receptors, Transferrin --- Protein Translocation Systems --- Biological Transport --- Bacterial Secretion Systems --- Biocatalyst --- Enzyme --- Heterotrimeric G Protein --- G Protein, Heterotrimeric --- Protein, Heterotrimeric G --- Hydrolase --- Peptide --- Polypeptide --- Protein --- Cell Membrane Protein --- Cell Surface Protein --- Membrane-Associated Protein --- Surface Protein --- Membrane Associated Protein --- Membrane Protein, Cell --- Protein, Cell Membrane --- Protein, Cell Surface --- Protein, Membrane-Associated --- Protein, Surface --- Surface Protein, Cell --- Carrier Protein --- Transport Protein --- Protein, Carrier --- Protein, Transport --- Membrane Transport Protein --- Membrane Transporter --- Permease --- Protein, Membrane Transport --- Transport Protein, Membrane --- Transporter, Membrane --- Gtp-binding proteins --- Signal transduction --- Membrane proteins.

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