BACKGROUND-AIM Nowadays, antibiotic resistance is a major public health issue, with an increasing number of pathogens becoming capable of eluding conventional Antibiotic therapies. This becomes crucially relevant when applied to symbiotic bacteria such E. coli, a typical symbiont of the colonic mucosa. The relation between E. coli and antibiotic resistant E. coli and its possible modulation on pathways of proliferation and differentiation hasn’t been explored widely. Our study aims at evaluating how E. coli and Carbapenemase E. coli may affect renovation/differentiation signals of the colonic mucosa, with a focus on the WNT/β catenin pathway. METHODS Colonic epithelial cells, Caco-2, were treated in the proliferation phase (3 d.o.) and differentiation phase (16 d.o.) with graded dilutions of bacteria in E. coli (ATCC 35218) and E. coli carbapenemase (ATCC 25922) culture broth, selected from current literature. We assessed epithelial cell viability by MTS; WNT-β catenin signaling modulation of gene expression by RT-PCR. Cell cycle and extracellular vesicles (EVs) analysis were also performed. RESULTS Exposure of colon epithelial cells to the broth of the two E. coli strains caused a modulation of cell viability and mitochondrial metabolism, as well as the production of EVs. Gene expression of molecules downstream of the WNT signal, such as APC, LEF1, JUN/AP1, CXCL8, CDND1 and cMYC, was significantly different. Furthermore, in proliferating cells the effects of exposure to E.Coli antibiotic-resistant were significantly different than in differentiated cells. CONCLUSIONS In this study, we observed that antibiotic-resistant E. coli products can modulate the WNT/β-Catenin signal of colon epithelium renewal. Further clinical and experimental observations will be necessary to obtain a clearer picture of the interactions between antibiotic-resistant E. coli and the pathophysiology of the colon epithelium.

P196 ANTIBIOTIC RESISTANT E. COLI CAN MODULATE RENEWAL/DIFFERENTIATION SIGNALS OF THE COLON MUCOSA: FOCUS ON THE WNT/β CATENIN PATHWAY

Francesca D’Ascanio;Annalisa Giardinelli;Vincenzo Ferrone;Ivana Cataldo;Paola Lanuti;Gambi Alessandra
Penultimo
;
Aceto Gitana Maria
Ultimo
2024-01-01

Abstract

BACKGROUND-AIM Nowadays, antibiotic resistance is a major public health issue, with an increasing number of pathogens becoming capable of eluding conventional Antibiotic therapies. This becomes crucially relevant when applied to symbiotic bacteria such E. coli, a typical symbiont of the colonic mucosa. The relation between E. coli and antibiotic resistant E. coli and its possible modulation on pathways of proliferation and differentiation hasn’t been explored widely. Our study aims at evaluating how E. coli and Carbapenemase E. coli may affect renovation/differentiation signals of the colonic mucosa, with a focus on the WNT/β catenin pathway. METHODS Colonic epithelial cells, Caco-2, were treated in the proliferation phase (3 d.o.) and differentiation phase (16 d.o.) with graded dilutions of bacteria in E. coli (ATCC 35218) and E. coli carbapenemase (ATCC 25922) culture broth, selected from current literature. We assessed epithelial cell viability by MTS; WNT-β catenin signaling modulation of gene expression by RT-PCR. Cell cycle and extracellular vesicles (EVs) analysis were also performed. RESULTS Exposure of colon epithelial cells to the broth of the two E. coli strains caused a modulation of cell viability and mitochondrial metabolism, as well as the production of EVs. Gene expression of molecules downstream of the WNT signal, such as APC, LEF1, JUN/AP1, CXCL8, CDND1 and cMYC, was significantly different. Furthermore, in proliferating cells the effects of exposure to E.Coli antibiotic-resistant were significantly different than in differentiated cells. CONCLUSIONS In this study, we observed that antibiotic-resistant E. coli products can modulate the WNT/β-Catenin signal of colon epithelium renewal. Further clinical and experimental observations will be necessary to obtain a clearer picture of the interactions between antibiotic-resistant E. coli and the pathophysiology of the colon epithelium.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11564/865953
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