PMID- 35931114
OWN - NLM
STAT- MEDLINE
DCOM- 20220929
LR  - 20221018
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 298
IP  - 9
DP  - 2022 Sep
TI  - Chlamydia trachomatis development requires both host glycolysis and oxidative 
      phosphorylation but has only minor effects on these pathways.
PG  - 102338
LID - S0021-9258(22)00780-3 [pii]
LID - 10.1016/j.jbc.2022.102338 [doi]
LID - 102338
AB  - 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 2 cell lines of nontumoral origin, we showed 
      that between the 2 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.
CI  - Copyright (c) 2022 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - N'Gadjaga, Maimouna D
AU  - N'Gadjaga MD
AD  - Institut Pasteur, CNRS UMR3691, Cellular Biology of Microbial Infection, 
      Universite Paris Cite, Paris, France; Sorbonne Universite, College Doctoral, 
      Paris, France.
FAU - Perrinet, Stephanie
AU  - Perrinet S
AD  - Institut Pasteur, CNRS UMR3691, Cellular Biology of Microbial Infection, 
      Universite Paris Cite, Paris, France.
FAU - Connor, Michael G
AU  - Connor MG
AD  - Institut Pasteur, Chromatin and Infection, Universite Paris Cite, Paris, France.
FAU - Bertolin, Giulia
AU  - Bertolin G
AD  - CNRS, IGDR (Institute of Genetics and Development of Rennes), UMR 6290, Univ 
      Rennes, Rennes, France.
FAU - Millot, Gael A
AU  - Millot GA
AD  - Institut Pasteur, Hub Bioinformatique et Biostatistique-DBC, Universite Paris 
      Cite, Paris, France.
FAU - Subtil, Agathe
AU  - Subtil A
AD  - Institut Pasteur, CNRS UMR3691, Cellular Biology of Microbial Infection, 
      Universite Paris Cite, Paris, France. Electronic address: asubtil@pasteur.fr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220802
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - *Chlamydia Infections/metabolism/microbiology
MH  - *Chlamydia trachomatis/growth & development/metabolism
MH  - *Epithelial Cells/metabolism/microbiology
MH  - Glucose/metabolism
MH  - *Glycolysis
MH  - HeLa Cells
MH  - *Host-Pathogen Interactions
MH  - Humans
MH  - *Oxidative Phosphorylation
PMC - PMC9449673
OTO - NOTNLM
OT  - ATP
OT  - Chlamydia trachomatis
OT  - glycolysis
OT  - host-pathogen interaction
OT  - metabolism
OT  - oxidative phosphorylation
COIS- Conflict of interest The authors declare that they have no conflict of interest 
      with the contents of this article.
EDAT- 2022/08/06 06:00
MHDA- 2022/09/30 06:00
PMCR- 2022/08/02
CRDT- 2022/08/05 19:22
PHST- 2022/06/11 00:00 [received]
PHST- 2022/07/27 00:00 [revised]
PHST- 2022/07/28 00:00 [accepted]
PHST- 2022/08/06 06:00 [pubmed]
PHST- 2022/09/30 06:00 [medline]
PHST- 2022/08/05 19:22 [entrez]
PHST- 2022/08/02 00:00 [pmc-release]
AID - S0021-9258(22)00780-3 [pii]
AID - 102338 [pii]
AID - 10.1016/j.jbc.2022.102338 [doi]
PST - ppublish
SO  - J Biol Chem. 2022 Sep;298(9):102338. doi: 10.1016/j.jbc.2022.102338. Epub 2022 
      Aug 2.