Association of colorectal cancer with pathogenic Escherichia coli: Focus on mechanisms using optical imaging.
OBJECTIVE
To investigate the molecular or cellular mechanisms related to the infection of epithelial colonic mucosa by pks-positive Escherichia coli (E. coli) using optical imaging.


METHODS
We choose to evaluate the tumor metabolic activity using a fluorodeoxyglucose analogue as 2-deoxyglucosone fluorescent probes and to correlate it with tumoral volume (mm(3)). Inflammation measuring myeloperoxidase (MPO) activity and reactive oxygen species production was monitored by a bioluminescent (BLI) inflammation probe and related to histological examination and MPO levels by enzyme-linked immunosorbent assay (ELISA) on tumor specimens. The detection and quantitation of these two signals were validated on a xenograft model of human colon adenocarcinoma epithelial cells (HCT116) in nude mice infected with a pks-positive E. coli. The inflammatory BLI signal was validated intra-digestively in the colitis-CEABAC10 DSS models, which mimicked Crohn's disease.


RESULTS
Using a 2-deoxyglucosone fluorescent probe, we observed a high and specific HCT116 tumor uptake in correlation with tumoral volume (P = 0.0036). Using the inflammation probe targeting MPO, we detected a rapid systemic elimination and a significant increase of the BLI signal in the pks-positive E. coli-infected HCT116 xenograft group (P < 0.005). ELISA confirmed that MPO levels were significantly higher (1556 ± 313.6 vs 234.6 ± 121.6 ng/mL P = 0.001) in xenografts infected with the pathogenic E. coli strain. Moreover, histological examination of tumor samples confirmed massive infiltration of pks-positive E. coli-infected HCT116 tumors by inflammatory cells compared to the uninfected group. These data showed that infection with the pathogenic E. coli strain enhanced inflammation and ROS production in tumors before tumor growth. Moreover, we demonstrated that the intra-digestive monitoring of inflammation is feasible in a reference colitis murine model (CEABAC10/DSS).


CONCLUSIONS
Using BLI and fluorescence optical imaging, we provided tools to better understand host-pathogen interactions at the early stage of disease, such as inflammatory bowel disease and colorectal cancer.
Julie Veziant, Johan Gagnière, Virginie Bonnin, Pierre Sauvanet, Denis Pezet, Nicolas Barnich, Mathilde Bonnet, UMR1071 Inserm/Université d'Auvergne and INRA USC2018, Clermont Université, 63000 Clermont-Ferrand, France.
Julie
J
Veziant
Julie Veziant, Johan Gagnière, Virginie Bonnin, Pierre Sauvanet, Denis Pezet, Nicolas Barnich, Mathilde Bonnet, UMR1071 Inserm/Université d'Auvergne and INRA USC2018, Clermont Université, 63000 Clermont-Ferrand, France.
Johan
J
Gagnière
Julie Veziant, Johan Gagnière, Virginie Bonnin, Pierre Sauvanet, Denis Pezet, Nicolas Barnich, Mathilde Bonnet, UMR1071 Inserm/Université d'Auvergne and INRA USC2018, Clermont Université, 63000 Clermont-Ferrand, France.
Elodie
E
Jouberton
Julie Veziant, Johan Gagnière, Virginie Bonnin, Pierre Sauvanet, Denis Pezet, Nicolas Barnich, Mathilde Bonnet, UMR1071 Inserm/Université d'Auvergne and INRA USC2018, Clermont Université, 63000 Clermont-Ferrand, France.
Virginie
V
Bonnin
Julie Veziant, Johan Gagnière, Virginie Bonnin, Pierre Sauvanet, Denis Pezet, Nicolas Barnich, Mathilde Bonnet, UMR1071 Inserm/Université d'Auvergne and INRA USC2018, Clermont Université, 63000 Clermont-Ferrand, France.
Pierre
P
Sauvanet
Julie Veziant, Johan Gagnière, Virginie Bonnin, Pierre Sauvanet, Denis Pezet, Nicolas Barnich, Mathilde Bonnet, UMR1071 Inserm/Université d'Auvergne and INRA USC2018, Clermont Université, 63000 Clermont-Ferrand, France.
Denis
D
Pezet
Julie Veziant, Johan Gagnière, Virginie Bonnin, Pierre Sauvanet, Denis Pezet, Nicolas Barnich, Mathilde Bonnet, UMR1071 Inserm/Université d'Auvergne and INRA USC2018, Clermont Université, 63000 Clermont-Ferrand, France.
Nicolas
N
Barnich
Julie Veziant, Johan Gagnière, Virginie Bonnin, Pierre Sauvanet, Denis Pezet, Nicolas Barnich, Mathilde Bonnet, UMR1071 Inserm/Université d'Auvergne and INRA USC2018, Clermont Université, 63000 Clermont-Ferrand, France.
Elisabeth
E
Miot-Noirault
Julie Veziant, Johan Gagnière, Virginie Bonnin, Pierre Sauvanet, Denis Pezet, Nicolas Barnich, Mathilde Bonnet, UMR1071 Inserm/Université d'Auvergne and INRA USC2018, Clermont Université, 63000 Clermont-Ferrand, France.
Mathilde
M
Bonnet
Colibactin; Colorectal carcinoma; Escherichia coli; In vivo optical imaging; Myeloperoxidase