Title :

The colibactin-producing <i>Escherichia coli</i> alters the tumor microenvironment to immunosuppressive lipid overload facilitating colorectal cancer progression and chemoresistance.

Author(s) :

De Oliveira Alves Brito, Nilmara [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Dalmasso, Guillaume [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Nikitina, D. [Auteur]
Vaysse, A. [Auteur]
Ruez, Richard [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Ledoux, Léa [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 [PRISM]
Pedron, T. [Auteur]
Bergsten, E. [Auteur]
Boulard, Olivier [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Autier, Laura [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Allam, Sofian [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Motreff, L. [Auteur]
Sauvanet, P. [Auteur]
Letourneur, D. [Auteur]
Kashyap, P. [Auteur]
Gagnière, J. [Auteur]
Pezet, D. [Auteur]
Godfraind, C. [Auteur]
Salzet, Michel [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Lemichez, E. [Auteur]
Bonnet, M. [Auteur]
Najjar, I. [Auteur]
Malabat, C. [Auteur]
Monot, M. [Auteur]
Mestivier, D. [Auteur]
Barnich, N. [Auteur]
Yadav, P. [Auteur]
Fournier, Isabelle [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 [PRISM]
Kennedy, S. [Auteur]
Mettouchi, A. [Auteur]
Bonnet, R. [Auteur]
Sobhani, I. [Auteur]
Chamaillard, Mathias [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]

Journal title :

Gut Microbes

Abbreviated title :

Gut Microbes

Volume number :

16

Pages :

2320291

Publisher :

Taylor & Francis Online

Publication date :

2024-02-29

ISSN :

1949-0984

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Intratumoral bacteria flexibly contribute to cellular and molecular tumor heterogeneity for supporting cancer recurrence through poorly understood mechanisms. Using spatial metabolomic profiling technologies and 16SrRNA ...
Show more >Intratumoral bacteria flexibly contribute to cellular and molecular tumor heterogeneity for supporting cancer recurrence through poorly understood mechanisms. Using spatial metabolomic profiling technologies and 16SrRNA sequencing, we herein report that right-sided colorectal tumors are predominantly populated with Colibactin-producing Escherichia coli (CoPEC) that are locally establishing a high-glycerophospholipid microenvironment with lowered immunogenicity. It coincided with a reduced infiltration of CD8+ T lymphocytes that produce the cytotoxic cytokines IFN-γ where invading bacteria have been geolocated. Mechanistically, the accumulation of lipid droplets in infected cancer cells relied on the production of colibactin as a measure to limit genotoxic stress to some extent. Such heightened phosphatidylcholine remodeling by the enzyme of the Land’s cycle supplied CoPEC-infected cancer cells with sufficient energy for sustaining cell survival in response to chemotherapies. This accords with the lowered overall survival of colorectal patients at stage III-IV who were colonized by CoPEC when compared to patients at stage I-II. Accordingly, the sensitivity of CoPEC-infected cancer cells to chemotherapies was restored upon treatment with an acyl-CoA synthetase inhibitor. By contrast, such metabolic dysregulation leading to chemoresistance was not observed in human colon cancer cells that were infected with the mutant strain that did not produce colibactin (11G5∆ClbQ). This work revealed that CoPEC locally supports an energy trade-off lipid overload within tumors for lowering tumor immunogenicity. This may pave the way for improving chemoresistance and subsequently outcome of CRC patients who are colonized by CoPEC.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192

Submission date :

2024-03-12T22:15:56Z
2024-05-22T09:10:27Z