1. Solid tumors provide niche-specific conditions that lead to preferential growth of Salmonella
- Author
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Prerak T. Desai, Carlos A. Santiviago, Steffen Porwollik, Cecilia A. Silva-Valenzuela, Robert M. Hoffman, David Pezoa, Yong Zhang, Inés Contreras, Michael McClelland, Roberto C. Molina-Quiroz, and Ming Zhao
- Subjects
0301 basic medicine ,Salmonella typhimurium ,Salmonella ,Mutant ,medicine.disease_cause ,4T1 ,Mice ,0302 clinical medicine ,mammary cancer ,2.1 Biological and endogenous factors ,Colonization ,Aetiology ,Inbred BALB C ,high-throughput ,Cancer ,Mice, Inbred BALB C ,Bacterial ,High-Throughput Nucleotide Sequencing ,Foodborne Illness ,Infectious Diseases ,Oncology ,030220 oncology & carcinogenesis ,Salmonella Infections ,Female ,Research Paper ,ethanolamine ,Oncology and Carcinogenesis ,Motility ,Biology ,Microbiology ,Vaccine Related ,Experimental ,03 medical and health sciences ,Breast cancer ,Breast Cancer ,Genetics ,medicine ,Animals ,Gene ,Salmonella Infections, Animal ,Animal ,Prevention ,Mammary Neoplasms ,Mammary Neoplasms, Experimental ,Chemotaxis ,medicine.disease ,Metabolic pathway ,Emerging Infectious Diseases ,030104 developmental biology ,Genes ,Genes, Bacterial ,Digestive Diseases - 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.
- Published
- 2016