Tumor-specific colonization, tissue distribution, and gene induction by probiotic Escherichia coli Nissle 1917 in live mice

Systemic administration of microorganisms into tumor-bearing mice revealed preferential accumulation in tumors in comparison to clearance in organs such as spleen and liver. Here we compared the efficiency of tumor-specific colonization of pathogenic Salmonella typhimurium strains 14028 and SL1344 to the enteroinvasive Escherichia coli 4608-58 strain and to the attenuated Salmonella flexneri 2a SC602 strain, as well as to the uropathogenic E. coli CFT073, the non-pathogenic E coli Top10, and the probiotic E coli Nissle 1917 strain. All strains colonized and replicated in tumors efficiently each resulting in more than 1 x 10(8) colony-forming units per gram tumor tissue. Colonization of spleen and liver were significantly lower when E coli strains were used in comparison to S. typhimurium and the non-pathogenic strains did not colonize those organs at all. Further investigation of E coli Nissle 1917 showed that no drastic differences in colonization and amplification were seen when immunocompetent and immunocompromised animals were used, and we were able to show that E coli Nissle 1917 replicates at the border of live and necrotic tumor tissue. We also demonstrated exogenously applied L-arabinose-dependent gene activation in colonized tumors in live mice. These findings will prepare the way for bacterium-mediated controlled protein delivery to solid tumors. (C) 2007 Elsevier GmbH. All rights reserved.