Solid tumors provide niche-specific conditions that lead to preferential growth of Salmonella
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Cecilia A. Silva-Valenzuela1,2,3, Prerak T. Desai1, Roberto C. Molina-Quiroz2,4, David Pezoa2, Yong Zhang5, Steffen Porwollik1, Ming Zhao5, Robert M. Hoffman5,6, Inés Contreras2, Carlos A. Santiviago2, Michael McClelland1
1Department of Microbiology and Molecular Genetics, University of California, Irvine, CA, USA
2Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile
3Current address: Department of Molecular Biology and Microbiology, Tufts University, Boston, MA, USA
4Current address: Center for Adaptation Genetics and Drug Resistance, Tufts University, Boston, MA, USA
5AntiCancer, Inc., San Diego, CA, USA
6Department of Surgery, University of California, San Diego, CA, USA
Carlos A. Santiviago, e-mail: [email protected]
Michael McClelland, e-mail: [email protected]
Keywords: Salmonella Typhimurium, ethanolamine, high-throughput, mammary cancer, 4T1
Received: November 4, 2015 Accepted: April 10, 2016 Published: April 28, 2016
Therapeutic attenuated strains of Salmonella Typhimurium target and eradicate tumors in mouse models. However, the mechanism of S. Typhimurium for tumor targeting is still poorly understood. We performed a high-throughput screening of single-gene deletion mutants of S. Typhimurium in an orthotopic, syngeneic murine mammary model of breast cancer. The mutants under selection in this system were classified into functional categories to identify bacterial processes involved in Salmonella accumulation within tumors. Niche-specific genes involved in preferential tumor colonization were identified and exemplars were confirmed by competitive infection assays. Our results show that the chemotaxis gene cheY and the motility genes motAB confer an advantage for colonization of Salmonella within orthotopic syngeneic breast tumors. In addition, eutC, a gene belonging to the ethanolamine metabolic pathway, also confers an advantage for Salmonella within tumors, perhaps by exploiting either ethanolamine or an alternative nutrient in the inflamed tumor environment.
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