Reprogramming of host glutamine metabolism during Chlamydia trachomatis infection and its key role in peptidoglycan synthesis.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Wulff, Thomas F
Dejure, Francesca R
MetadataShow full item record
AbstractObligate intracellular bacteria such as Chlamydia trachomatis undergo a complex developmental cycle between infectious, non-replicative elementary-body and non-infectious, replicative reticulate-body forms. Elementary bodies transform to reticulate bodies shortly after entering a host cell, a crucial process in infection, initiating chlamydial replication. As Chlamydia fail to replicate outside the host cell, it is unknown how the replicative part of the developmental cycle is initiated. Here we show, using a cell-free approach in axenic media, that the uptake of glutamine by the bacteria is crucial for peptidoglycan synthesis, which has a role in Chlamydia replication. The increased requirement for glutamine in infected cells is satisfied by reprogramming the glutamine metabolism in a c-Myc-dependent manner. Glutamine is effectively taken up by the glutamine transporter SLC1A5 and metabolized via glutaminase. Interference with this metabolic reprogramming limits the growth of Chlamydia. Intriguingly, Chlamydia failed to produce progeny in SLC1A5-knockout organoids and mice. Thus, we report on the central role of glutamine for the development of an obligate intracellular pathogenic bacterium and the reprogramming of host glutamine metabolism, which may provide a basis for innovative anti-infection strategies.
CitationNat Microbiol. 2020 Nov;5(11):1390-1402. doi: 10.1038/s41564-020-0762-5.
AffiliationHIRI, Helmholtz-Institut für RNA-basierte Infektionsforschung, Josef-Shneider Strasse 2, 97080 Würzburg, Germany.
PublisherNature publishing group (NPG)
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International
- Metabolic adaptation of Chlamydia trachomatis to mammalian host cells.
- Authors: Mehlitz A, Eylert E, Huber C, Lindner B, Vollmuth N, Karunakaran K, Goebel W, Eisenreich W, Rudel T
- Issue date: 2017 Mar
- A Dynamic, Ring-Forming Bactofilin Critical for Maintaining Cell Size in the Obligate Intracellular Bacterium Chlamydia trachomatis.
- Authors: Brockett MR, Lee J, Cox JV, Liechti GW, Ouellette SP
- Issue date: 2021 Jul 15
- Chlamydia trachomatis Prevents Apoptosis Via Activation of PDPK1-MYC and Enhanced Mitochondrial Binding of Hexokinase II.
- Authors: Al-Zeer MA, Xavier A, Abu Lubad M, Sigulla J, Kessler M, Hurwitz R, Meyer TF
- Issue date: 2017 Sep
- SLC1A5 glutamine transporter is a target of MYC and mediates reduced mTORC1 signaling and increased fatty acid oxidation in long-lived Myc hypomorphic mice.
- Authors: Zhao X, Petrashen AP, Sanders JA, Peterson AL, Sedivy JM
- Issue date: 2019 Jun
- Fosmidomycin, an inhibitor of isoprenoid synthesis, induces persistence in Chlamydia by inhibiting peptidoglycan assembly.
- Authors: Slade JA, Brockett M, Singh R, Liechti GW, Maurelli AT
- Issue date: 2019 Oct