title: Solid tumors provide niche-specific conditions that lead to preferential growth of Salmonella.
abstract: 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.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of California, Irvine, CA, USA.|Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.|Current address: Department of Molecular Biology and Microbiology, Tufts University, Boston, MA, USA.
authors.forename: Cecilia A
authors.initials: CA
authors.lastname: Silva-Valenzuela
authors.affiliation: Department of Microbiology and Molecular Genetics, University of California, Irvine, CA, USA.
authors.forename: Prerak T
authors.initials: PT
authors.lastname: Desai
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.|Current address: Center for Adaptation Genetics and Drug Resistance, Tufts University, Boston, MA, USA.
authors.forename: Roberto C
authors.initials: RC
authors.lastname: Molina-Quiroz
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.
authors.forename: David
authors.initials: D
authors.lastname: Pezoa
authors.affiliation: AntiCancer, Inc., San Diego, CA, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Microbiology and Molecular Genetics, University of California, Irvine, CA, USA.
authors.forename: Steffen
authors.initials: S
authors.lastname: Porwollik
authors.affiliation: AntiCancer, Inc., San Diego, CA, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.affiliation: AntiCancer, Inc., San Diego, CA, USA.|Department of Surgery, University of California, San Diego, CA, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.
authors.forename: Inés
authors.initials: I
authors.lastname: Contreras
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Santiviago
authors.affiliation: Department of Microbiology and Molecular Genetics, University of California, Irvine, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: McClelland
mesh_terms: D000818:Animals; D005260:Female; D005798:Genes, Bacterial / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D008325:Mammary Neoplasms, Experimental / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012481:Salmonella Infections, Animal / Q000235:genetics*; D012486:Salmonella typhimurium / Q000235:genetics* / Q000254:growth & development*
keywords: 4T1; Salmonella Typhimurium; ethanolamine; high-throughput; mammary cancer