Non-typhoidal Salmonella infections can promote cell transformation and colon cancer progression

Non-typhoidal Salmonella (NTS) are facultative intracellular pathogens that can promote cell transformation and are associated epidemiologically and experimentally with colon cancer development. Yet, the driving factors of Salmonella-induced cell transformation are mostly unknown. Here, we observed that NTS-associated colon tumors had generally a lower pathological grading suggesting a different biology of the Salmonella-associated tumors. We studied NTS clinical strains isolated from patients who were diagnosed with colon cancer more than a year after Salmonella infection, versus control patients. We characterized the different Salmonella clinical strains for a series of features including their efficiency to invade and transform mammalian cells, aligned with their genome, transcriptome, and capacity to replicate in various conditions. The clinical strains displayed diverse infection and transformation efficiencies albeit both processes were related. The transformation efficiency could not be attributed to specific DNA features but could be associated with specific gene expression, in particular metabolic genes and regulons. Besides, metabolic phenotyping showed that NTS strains with a higher transformation efficiency display an increased capacity to utilize various nutrient sources, including carbohydrates and amino acids. Finally, high-transforming NTS strains grow significantly faster intracellularly than low-transforming NTS, using both vacuolar and cytosolic niches. This study highlights the presence of highly transforming NTS within the human population and links transformation efficiency with bacterial transcriptome profile, phenotypic behavior, and intracellular pathogenicity.