1. Transketolase of Staphylococcus aureus in the Control of Master Regulators of Stress Response During Infection
- Author
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Elodie Ramond, Xin Tan, Fabiola Tros, Jean-Philippe Barnier, Daniel Euphrasie, Jason Ziveri, Ivan Nemazanyy, Xavier Nassif, Anne Jamet, Baptiste Decaux-Tramoni, Alain Charbit, Marion Dupuis, Mathieu Coureuil, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Pathogénie des infections systémiques (Inserm U1002), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Pharmacovigilance (CRPV), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), SOGIP, SOGIP (ERC 249236)/Laboratoire d'Anthropologie des Institutions et des Organisations Sociales (IIAC-LAIOS), Institut interdisciplinaire d'anthropologie du contemporain (IIAC), École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS)-Institut interdisciplinaire d'anthropologie du contemporain (IIAC), École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), U1002, Pathogénie des infections systémiques (UMR_S 570), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (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)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Charbit, Alain
- Subjects
0301 basic medicine ,Staphylococcus aureus ,RNAIII ,030106 microbiology ,Mutant ,pentose phosphate pathway ,Transketolase ,Biology ,Pentose phosphate pathway ,Kidney ,medicine.disease_cause ,Microbiology ,Mice ,03 medical and health sciences ,Stress, Physiological ,sigma B ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Transcription (biology) ,RpiRc ,medicine ,Animals ,Humans ,Metabolomics ,Immunology and Allergy ,Gene Silencing ,Gene ,ComputingMilieux_MISCELLANEOUS ,Gene Expression Profiling ,metabolic adaptation ,Gene Expression Regulation, Bacterial ,Staphylococcal Infections ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,Carbon ,3. Good health ,Disease Models, Animal ,Phenotype ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,030104 developmental biology ,Infectious Diseases ,Genes, Bacterial ,Mutation ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,transketolase ,[SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,Intracellular ,Signal Transduction - Abstract
Staphylococcus aureus is a leading cause of both acute and chronic infections in humans. The importance of the pentose phosphate pathway (PPP) during S. aureus infection is currently largely unexplored. In the current study, we focused on one key PPP enzyme, transketolase (TKT). We showed that inactivation of the unique gene encoding TKT activity in S. aureus USA300 (∆tkt) led to drastic metabolomic changes. Using time-lapse video imaging and mice infection, we observed a major defect of the ∆tkt strain compared with wild-type strain in early intracellular proliferation and in the ability to colonize kidneys. Transcriptional activity of the 2 master regulators sigma B and RpiRc was drastically reduced in the ∆tkt mutant during host cells invasion. The concomitant increased RNAIII transcription suggests that TKT—or a functional PPP—strongly influences the ability of S. aureus to proliferate within host cells by modulating key transcriptional regulators.
- Published
- 2019
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