Antibiotic control of tumor-colonizing Salmonella enterica serovar Typhimurium.

Abstract

Systemic administration of Salmonella enterica serovar Typhimurium (S. typhimurium) into tumor-bearing mice results in preferential colonization of tumors and causes shrinkage and sometimes complete tumor clearance. However, in spite of these beneficial antitumor effects, the systemic administration of a bacterial pathogen raises serious safety concerns as well. Addressing those concerns, here, we demonstrate that tumor-colonizing Salmonella can be readily controlled by systemic administration of the antibiotic - ciprofloxacin. Treatment was most effective when started early postinfection. This was achieved at the expense of the efficacy of tumor therapy. In many of the mice treated in such a way, tumors re-grew again. Nevertheless, some mice were able to clear the tumor despite the start of antibiotic treatment only 24 h after the start of infection. Furthermore, we could demonstrate that such mice had elicited a specific antitumor immune response. Thus, S. typhimurium-mediated tumor therapy might be applied safely when combined with early antibiotic treatment. However, the therapeutic power of the bacteria needs to be enhanced in order to provide a more effective therapeutic tool.