8 results on '"Mélanie Héry"'
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2. Specificities and Commonalities of Carbapenemase-Producing Escherichia coli Isolated in France from 2012 to 2015
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Rafael Patiño-Navarrete, Isabelle Rosinski-Chupin, Nicolas Cabanel, Pengdbamba Dieudonné Zongo, Mélanie Héry, Saoussen Oueslati, Delphine Girlich, Laurent Dortet, Rémy A. Bonnin, Thierry Naas, and Philippe Glaser
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drug resistance evolution ,emergence ,genomics ,multidrug resistance ,surveillance studies ,Microbiology ,QR1-502 - Abstract
ABSTRACT Carbapenemase-producing Escherichia coli (CP-Ec) represents a major public health threat with a risk of dissemination in the community as has occurred for lineages producing extended-spectrum β-lactamases. To characterize the extent of CP-Ec spread in France, isolates from screening and infection samples received at the French National Reference Center (F-NRC) laboratory for carbapenemase-producing Enterobacterales were investigated. A total of 691 CP-Ec isolates collected between 2012 and 2015 and 22 isolates collected before 2012 were fully sequenced. Analysis of their genome sequences revealed some disseminating multidrug-resistant (MDR) lineages frequently acquiring diverse carbapenemase genes mainly belonging to clonal complex 23 (CC23) (sequence type 410 [ST410]) and CC10 (ST10 and ST167) and sporadic isolates, including rare ST131 isolates (n = 17). However, the most represented sequence type (ST) was ST38 (n = 92) with four disseminated lineages carrying blaOXA-48-like genes inserted in the chromosome. Globally, the most frequent carbapenemase gene (n = 457) was blaOXA-48. It was also less frequently associated with MDR isolates being the only resistance gene in 119 isolates. Thus, outside the ST38 clades, its acquisition was frequently sporadic with no sign of dissemination, reflecting the circulation of the IncL plasmid pOXA-48 in France and its high frequency of conjugation. In contrast, blaOXA-181 and blaNDM genes were often associated with the evolution of MDR E. coli lineages characterized by mutations in ftsI and ompC. IMPORTANCE Carbapenemase-producing Escherichia coli (CP-Ec) might be difficult to detect, as MICs can be very low. However, their absolute number and their proportion among carbapenem-resistant Enterobacterales have been increasing, as reported by WHO and national surveillance programs. This suggests a still largely uncharacterized community spread of these isolates. Here, we have characterized the diversity and evolution of CP-Ec isolated in France before 2016. We show that carbapenemase genes are associated with a wide variety of E. coli genomic backgrounds and a small number of dominant phylogenetic lineages. In a significant proportion of CP-Ec, the most frequent carbapenemase gene blaOXA-48, was detected in isolates lacking any other resistance gene, reflecting the dissemination of pOXA-48 plasmids, likely in the absence of any antibiotic pressure. In contrast, carbapenemase gene transfer may also occur in multidrug-resistant E. coli, ultimately giving rise to at-risk lineages encoding carbapenemases with a high potential of dissemination.
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- 2022
- Full Text
- View/download PDF
3. Specificities and commonalities of carbapenemase producing Escherichia coli isolated in France from 2012 to 2015
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Nicolas Cabanel, Isabelle Rosinski-Chupin, Delphine Girlich, Rémy A. Bonnin, Saoussen Oueslati, Laurent Dortet, Pengdbamba Dieudonné Zongo, Mélanie Héry, Rafael Patiño-Navarrete, Thierry Naas, Philippe Glaser, Ecologie et Evolution de la Résistance aux Antibiotiques / Ecology and Evolution of Antibiotics Resistance (EERA), Institut Pasteur [Paris]-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, French National Reference Center for Antibiotic Resistance: Carbapenemase producing Enterobacteriaceae [Le Kremlin-Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), This work was supported by grants from the French National Research Agency (ANR-10-LABX-62-IBEID, ANR-10-LABX-33, INCEPTION project (PIA/ANR-16-CONV-0005)) and from the European Union’s Horizon 2020 research and Innovation Program under grant agrement No 773830 (Project ARDIG, One Health EJP). Pengdbamba Dieudonné Zongo is a scholar of Ed525 CDV, Sorbonne Université, Paris., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-LABX-0033,LERMIT,Research Laboratory on Drugs and Therapeutic Innovation(2010), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), European Project: 773830,H2020-SFS-2017-1,MedVetKlebs (a component of European Joint Programme One Health EJP)(2018), and Institut Pasteur [Paris]-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC)
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Genetics ,0303 health sciences ,030306 microbiology ,Chromosome ,Carbapenemase producing ,Biology ,medicine.disease_cause ,Genome ,3. Good health ,Multiple drug resistance ,03 medical and health sciences ,Plasmid ,medicine ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Clade ,Escherichia coli ,Gene ,030304 developmental biology - Abstract
Carbapenemase-producing Escherichia coli (CP-Ec) represent a major public health threat with a risk of dissemination in the community as it has occurred for lineages producing extended spectrum ß-lactamases. To characterize the extend of CP-Ec spread in France, isolates from screening and infection samples received at the French National Reference Centre laboratory (F-NRC) for carbapenemase-producing Enterobacterales were investigated. Six hundred and ninety one CP-Ec isolates collected between 2012 and 2015 and 22 before were fully sequenced. Analysis of their genome sequences revealed some disseminating multidrug resistant (MDR) lineages frequently acquiring diverse carbapenemase genes mainly belonging to clonal complex (CC) 23 (ST 410) and CC10 (ST10, ST167) and sporadic isolates including rare ST131 isolates (n=17). However, the most represented ST was ST38 (n=92) with four disseminated lineages carrying blaOXA-48-like genes inserted in the chromosome. Globally, the most frequent carbapenemase gene (n=457) was blaOXA-48. It was also less frequently associated with MDR isolates being the only resistance gene in 119 isolates. Thus, outside the ST38 clades, its acquisition was frequently sporadic with no sign of dissemination, reflecting the circulation of the IncL plasmid pOXA-48 in France and its high frequency of conjugation. In contrast blaOXA-181 or blaNDM genes were often associated with the evolution of MDR E. coli lineages characterized by mutations in ftsI and ompC.IMPORTANCECarbapenemase-producing Escherichia coli (CP-Ec) might be difficult to detect, as minimal inhibitory concentrations can be very low. However, their absolute number and their proportion among carbapenem-resistant Enterobacterales have been increasing, as reported by WHO and national surveillance programs. This suggests a still largely uncharacterized community spread of these isolates. Here we have characterized the diversity and evolution of CP-Ec isolated in France before 2016. We show that carbapenemase genes are associated with a wide variety of E. coli genomic backgrounds and a small number of dominant phylogenetic lineages. In a significant proportion of CP-Ec, the most frequent carbapenemase gene blaOXA-48, was detected in isolates lacking any other resistance gene, reflecting the dissemination of pOXA-48 plasmids, likely in the absence of any antibiotic pressure. In contrast carbapenemase gene transfer may also occur in multi-drug resistant E. coli, ultimately giving rise to at-risk lineages encoding carbapenemases with a high potential of dissemination.
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- 2022
4. Functional assessment and phenotypic heterogeneity of SFTPA1 and SFTPA2 mutations in interstitial lung diseases and lung cancer
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Emilie Filhol-Blin, Serge Amselem, Vincent Cottin, Diane Bouvry, J. Bermudez, Bérénice Doray, Martine Reynaud-Gaubert, Violaine Giraud, Julie Traclet, Aurélie Le Borgne, Clairelyne Dupin, Sylvie Leroy, Nathalie Allou, Paul De Vuyst, Anne Bergeron, Anne-Laure Chene, Aurore Coulomb L'Hermine, Bruno Crestani, Raphael Borie, Clément Picard, Mélanie Héry, Anne Gondouin, Bruno Copin, Tifenn Desroziers, Elisabeth Longchampt, Philippe Duquesnoy, Jean-Charles Dalphin, Valérie Nau, Annick Clement, Dominique Israël-Biet, Christine Dombret, Caroline Kannengiesser, Gwenael Lorillon, Marie Legendre, Nadia Nathan, Afifaa Butt, Aurélie Cazes, Florence Dastot-Le Moal, Hilario Nunes, Marie-Pierre Debray, Laurent Gouya, Maladies génétiques d'expression pédiatrique (U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hypoxie et Poumon : pneumopathologies fibrosantes, modulations ventilatoires et circulatoires (H&P), UFR SMBH-Université Sorbonne Paris Nord, Hôpital Avicenne [AP-HP], Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], Hopital Saint-Louis [AP-HP] (AP-HP), Hôpital Nord [CHU - APHM], Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Centre hospitalier universitaire de Nantes (CHU Nantes), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital Ambroise Paré [AP-HP], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Pasteur [Nice] (CHU), Hôpital Foch [Suresnes], Hôpital Erasme [Bruxelles], Couvet, Sandrine, Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), UF de Génétique moléculaire [CHU Trousseau], Centre de référence national pour les maladies respiratoires rares de l’enfant RespiRare [CHU Trousseau], Service de Pneumologie pédiatrique [CHU Trousseau], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP]
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0301 basic medicine ,Pulmonary and Respiratory Medicine ,Mutation ,Lung ,business.industry ,Genetic heterogeneity ,medicine.medical_treatment ,[SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics ,medicine.disease ,medicine.disease_cause ,Penetrance ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,030228 respiratory system ,SFTPA2 ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,Immunology ,Medicine ,Adenocarcinoma ,Lung transplantation ,business ,Lung cancer - Abstract
IntroductionInterstitial lung diseases (ILDs) can be caused by mutations in the SFTPA1 and SFTPA2 genes, which encode the surfactant protein (SP) complex SP-A. Only 11 SFTPA1 or SFTPA2 mutations have so far been reported worldwide, of which five have been functionally assessed. In the framework of ILD molecular diagnosis, we identified 14 independent patients with pathogenic SFTPA1 or SFTPA2 mutations. The present study aimed to functionally assess the 11 different mutations identified and to accurately describe the disease phenotype of the patients and their affected relatives.MethodsThe consequences of the 11 SFTPA1 or SFTPA2 mutations were analysed both in vitro, by studying the production and secretion of the corresponding mutated proteins and ex vivo, by analysing SP-A expression in lung tissue samples. The associated disease phenotypes were documented.ResultsFor the 11 identified mutations, protein production was preserved but secretion was abolished. The expression pattern of lung SP-A available in six patients was altered and the family history reported ILD and/or lung adenocarcinoma in 13 out of 14 families (93%). Among the 28 SFTPA1 or SFTPA2 mutation carriers, the mean age at ILD onset was 45 years (range 0.6–65 years) and 48% underwent lung transplantation (mean age 51 years). Seven carriers were asymptomatic.DiscussionThis study, which expands the molecular and clinical spectrum of SP-A disorders, shows that pathogenic SFTPA1 or SFTPA2 mutations share similar consequences for SP-A secretion in cell models and in lung tissue immunostaining, whereas they are associated with a highly variable phenotypic expression of disease, ranging from severe forms requiring lung transplantation to incomplete penetrance.
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- 2020
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5. Functional assessment and phenotypic heterogeneity of
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Marie, Legendre, Afifaa, Butt, Raphaël, Borie, Marie-Pierre, Debray, Diane, Bouvry, Emilie, Filhol-Blin, Tifenn, Desroziers, Valérie, Nau, Bruno, Copin, Florence, Dastot-Le Moal, Mélanie, Héry, Philippe, Duquesnoy, Nathalie, Allou, Anne, Bergeron, Julien, Bermudez, Aurélie, Cazes, Anne-Laure, Chene, Vincent, Cottin, Bruno, Crestani, Jean-Charles, Dalphin, Christine, Dombret, Bérénice, Doray, Clairelyne, Dupin, Violaine, Giraud, Anne, Gondouin, Laurent, Gouya, Dominique, Israël-Biet, Caroline, Kannengiesser, Aurélie, Le Borgne, Sylvie, Leroy, Elisabeth, Longchampt, Gwenaël, Lorillon, Hilario, Nunes, Clément, Picard, Martine, Reynaud-Gaubert, Julie, Traclet, Paul, de Vuyst, Aurore, Coulomb L'Hermine, Annick, Clement, Serge, Amselem, and Nadia, Nathan
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Adult ,Lung Neoplasms ,Adolescent ,Pulmonary Surfactant-Associated Protein A ,Infant ,Middle Aged ,Young Adult ,Phenotype ,Child, Preschool ,Mutation ,Humans ,Child ,Lung Diseases, Interstitial ,Aged - Abstract
Interstitial lung diseases (ILDs) can be caused by mutations in theThe consequences of the 11For the 11 identified mutations, protein production was preserved but secretion was abolished. The expression pattern of lung SP-A available in six patients was altered and the family history reported ILD and/or lung adenocarcinoma in 13 out of 14 families (93%). Among the 28This study, which expands the molecular and clinical spectrum of SP-A disorders, shows that pathogenic
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- 2020
6. Low CCR5 expression protects HIV-specific CD4+ T cells of elite controllers from viral entry
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Mathieu Claireaux, Rémy Robinot, Jérôme Kervevan, Mandar Patgaonkar, Isabelle Staropoli, Anne Brelot, Alexandre Nouël, Stacy Gellenoncourt, Xian Tang, Mélanie Héry, Stevenn Volant, Emeline Perthame, Véronique Avettand-Fenoël, Julian Buchrieser, Thomas Cokelaer, Christiane Bouchier, Laurence Ma, Faroudy Boufassa, Samia Hendou, Valentina Libri, Milena Hasan, David Zucman, Pierre de Truchis, Olivier Schwartz, Olivier Lambotte, Lisa A. Chakrabarti, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Laboratoire de Microbiologie Clinique [AP-HP Hôpital Necker-Enfants Malades], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biomics (plateforme technologique), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Cytometrie et Biomarqueurs – Cytometry and Biomarkers (UTechS CB), Hôpital Foch [Suresnes], Hôpital Raymond Poincaré [AP-HP], Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université Paris-Sud - Paris 11 (UP11), This work was supported by grants to L.A.C. from ANRS (17218 and 19206), Institut Pasteur (PasteurInnov TETRHIS), and ANR (14 CE 16002901). The Biomics Platform is a member of the 'France Génomique' consortium (ANR10-INBS-09-08). M.C. was the recipient of a Sidaction fellowship, R.R. of a Pasteur Carnot MS and a Sidaction fellowships, M.P. of an ANRS fellowship, and S.G. of a MESR/Université de Paris fellowship., We are grateful to patients who participated in the study. We thank the investigators of the ANRS CO21 CODEX cohort and Camille Lecuroux for help with recruitment of controller patients, Morgane Marcou and Katia Bourdic for help with recruitment of treated patients, Bernard Lagane for the gift of plamids, and Sophie Novault from the Pasteur CB UTechS for advice on cell sorting. MHC class II tetramer reagents were provided by the NIH Tetramer Core facility at Emory University. The following reagent was obtained through the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH: HIV-1 PTE Gag peptide set (Cat # 11554)., ANR-14-CE16-0029,PD1VAX,Une nouvelle stratégie de vaccination par vecteur ADN PD1 pour mimer les réponses spécifiques de Gag trouvées chez les contrôleurs spontanés du VIH(2014), and ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010)
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CD4-Positive T-Lymphocytes ,Viral membrane fusion ,MESH: Mutation ,Receptors, CXCR3 ,Receptors, CCR5 ,Science ,MESH: Virus Internalization ,viruses ,General Physics and Astronomy ,Down-Regulation ,Gene Products, gag ,HIV Infections ,MESH: Receptors, CCR5 ,MESH: Down-Regulation ,General Biochemistry, Genetics and Molecular Biology ,Article ,MESH: Receptors, CXCR3 ,MESH: HIV-1 ,MESH: Elite Controllers ,Humans ,MESH: Humans ,Multidisciplinary ,Retrovirus ,Histocompatibility Antigens Class II ,MESH: CD4-Positive T-Lymphocytes ,virus diseases ,MESH: HIV Infections ,General Chemistry ,Virus Internalization ,MESH: Chemokines ,MESH: Gene Expression Regulation ,Gene Expression Regulation ,MESH: Gene Products, gag ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Mutation ,MESH: Histocompatibility Antigens Class II ,HIV-1 ,Chemokines ,Elite Controllers - Abstract
HIV elite controllers maintain a population of CD4 + T cells endowed with high avidity for Gag antigens and potent effector functions. How these HIV-specific cells avoid infection and depletion upon encounter with the virus remains incompletely understood. Ex vivo characterization of single Gag-specific CD4 + T cells reveals an advanced Th1 differentiation pattern in controllers, except for the CCR5 marker, which is downregulated compared to specific cells of treated patients. Accordingly, controller specific CD4 + T cells show decreased susceptibility to CCR5-dependent HIV entry. Two controllers carried biallelic mutations impairing CCR5 surface expression, indicating that in rare cases CCR5 downregulation can have a direct genetic cause. Increased expression of β-chemokine ligands upon high-avidity antigen/TCR interactions contributes to autocrine CCR5 downregulation in controllers without CCR5 mutations. These findings suggest that genetic and functional regulation of the primary HIV coreceptor CCR5 play a key role in promoting natural HIV control., Here, Claireaux et al. show that people who naturally control HIV infection express lower levels of the viral co-receptor CCR5 in specific CD4+ T cells, and that this results from mutations or receptor internalization by CD4+ T cell-produced chemokines.
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- 2019
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7. First outbreak of OXA-48-positive carbapenem-resistant Klebsiella pneumoniae isolates in Constantine, Algeria
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Farida Smati, Anaïs Vogel, Gaelle Cuzon, Chafia Bentchouala, Abdesselam Lezzar, Mélanie Héry, Laurent Dortet, and Thierry Naas
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Microbiology (medical) ,Adult ,Male ,Carbapenem resistant Klebsiella pneumoniae ,Klebsiella pneumoniae ,Outbreak ,General Medicine ,Klebsiella infections ,Biology ,Middle Aged ,biology.organism_classification ,beta-Lactamases ,Microbiology ,Anti-Bacterial Agents ,Disease Outbreaks ,Klebsiella Infections ,Infectious Diseases ,Carbapenems ,Algeria ,Drug Resistance, Multiple, Bacterial ,Humans ,Pharmacology (medical) ,Female ,Child - Published
- 2015
8. Tracking receptor motions at the plasma membrane reveals distinct effects of ligands on CCR5 dynamics depending on its dimerization status
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Fanny Momboisse, Giacomo Nardi, Philippe Colin, Melanie Hery, Nelia Cordeiro, Simon Blachier, Olivier Schwartz, Fernando Arenzana-Seisdedos, Nathalie Sauvonnet, Jean-Christophe Olivo-Marin, Bernard Lagane, Thibault Lagache, and Anne Brelot
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GPCR ,single-particle-tracking ,Dimerization ,chemokine receptor ,CCR5 ,imaging ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
G-protein-coupled receptors (GPCR) are present at the cell surface in different conformational and oligomeric states. However, how these states impact GPCRs biological function and therapeutic targeting remains incompletely known. Here, we investigated this issue in living cells for the CC chemokine receptor 5 (CCR5), a major receptor in inflammation and the principal entry co-receptor for Human Immunodeficiency Viruses type 1 (HIV-1). We used TIRF microscopy and a statistical method to track and classify the motion of different receptor subpopulations. We showed a diversity of ligand-free forms of CCR5 at the cell surface constituted of various oligomeric states and exhibiting transient Brownian and restricted motions. These forms were stabilized differently by distinct ligands. In particular, agonist stimulation restricted the mobility of CCR5 and led to its clustering, a feature depending on β-arrestin, while inverse agonist stimulation exhibited the opposite effect. These results suggest a link between receptor activation and immobilization. Applied to HIV-1 envelope glycoproteins gp120, our quantitative analysis revealed agonist-like properties of gp120s. Distinct gp120s influenced CCR5 dynamics differently, suggesting that they stabilize different CCR5 conformations. Then, using a dimerization-compromized mutant, we showed that dimerization (i) impacts CCR5 precoupling to G proteins, (ii) is a pre-requisite for the immobilization and clustering of receptors upon activation, and (iii) regulates receptor endocytosis, thereby impacting the fate of activated receptors. This study demonstrates that tracking the dynamic behavior of a GPCR is an efficient way to link GPCR conformations to their functions, therefore improving the development of drugs targeting specific receptor conformations.
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- 2022
- Full Text
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