Chlamydia trachomatis development requires both host glycolysis and oxidative phosphorylation but has only minor effects on these pathways

Autor: Maimouna D. N’Gadjaga, Stéphanie Perrinet, Michael G. Connor, Giulia Bertolin, Gaël A. Millot, Agathe Subtil
Přispěvatelé: Biologie cellulaire de l'Infection microbienne - Cellular Biology of Microbial Infection, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Collège Doctoral, Sorbonne Université (SU), Chromatine et Infection - Chromatin and Infection, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, This work was supported by the Fondation ARC pour la Recherche sur le Cancer, France, the Institut Pasteur, France (GPF-LINMEC grant METINFECT), les Entreprises contre le cancer (GEFLUC, France), and the Centre National de la Recherche Scientifique, France.
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Journal of Biological Chemistry
Journal of Biological Chemistry, 2022, 298 (9), pp.102338. ⟨10.1016/j.jbc.2022.102338⟩
ISSN: 0021-9258
1083-351X
DOI: 10.1016/j.jbc.2022.102338⟩
Popis: International audience; The obligate intracellular bacteria Chlamydia trachomatis obtain all nutrients from the cytoplasm of their epithelial host cells and stimulate glucose uptake by these cells. They even hijack host ATP, exerting a strong metabolic pressure on their host at the peak of the proliferative stage of their developmental cycle. However, it is largely unknown whether infection modulates the metabolism of the host cell. Also, the reliance of the bacteria on host metabolism might change during their progression through their biphasic developmental cycle. Herein, using primary epithelial cells and two cell lines of non-tumoral origin, we showed that between the two main ATP-producing pathways of the host, oxidative phosphorylation (OxPhos) remained stable and glycolysis was slightly increased. Inhibition of either pathway strongly reduced bacterial proliferation, implicating that optimal bacterial growth required both pathways to function at full capacity. While we found C. trachomatis displayed some degree of energetic autonomy in the synthesis of proteins expressed at the onset of infection, functional host glycolysis was necessary for the establishment of early inclusions, whereas OxPhos contributed less. These observations correlated with the relative contributions of the pathways in maintaining ATP levels in epithelial cells, with glycolysis contributing the most. Altogether, this work highlights the dependence of C. trachomatis on both host glycolysis and OxPhos for efficient bacterial replication. However, ATP consumption appears at equilibrium with the normal production capacity of the host and the bacteria, so that no major shift between these pathways is required to meet bacterial needs.
Databáze: OpenAIRE