Media Ion Composition Controls Regulatory and Virulence Response of Salmonella in Spaceflight

James W. Wilson, C. Mark Ott, Laura Quick, Richard Davis, Kerstin Höner zu Bentrup, Aurélie Crabbé, Emily Richter, Shameema Sarker, Jennifer Barrila, Steffen Porwollik, Pui Cheng, Michael McClelland, George Tsaprailis, Timothy Radabaugh, Andrea Hunt, Miti Shah, Mayra Nelman-Gonzalez, Steve Hing, Macarena Parra, Paula Dumars, Kelly Norwood, Ramona Bober, Jennifer Devich, Ashleigh Ruggles, Autumn CdeBaca, Satro Narayan, Joseph Benjamin, Carla Goulart, Mark Rupert, Luke Catella, Michael J. Schurr, Kent Buchanan, Lisa Morici, James McCracken, Marc D. Porter, Duane L. Pierson, Scott M. Smith, Max Mergeay, Natalie Leys, Heidemarie M. Stefanyshyn-Piper, Dominic Gorie, Cheryl A. Nickerson

The spaceflight environment is relevant to conditions encountered by pathogens during the course of infection and induces novel changes in microbial pathogenesis not observed using conventional methods. It is unclear how microbial cells sense spaceflight-associated changes to their growth environment and orchestrate corresponding changes in molecular and physiological phenotypes relevant to the infection process. Here we report that spaceflight-induced increases in Salmonella virulence are regulated by media ion composition, and that phosphate ion is sufficient to alter related pathogenesis responses in a spaceflight analogue model. Using whole genome microarray and proteomic analyses from two independent Space Shuttle missions, we identified evolutionarily conserved molecular pathways in Salmonella that respond to spaceflight under all media compositions tested. Identification of conserved regulatory paradigms opens new avenues to control microbial responses during the infection process and holds promise to provide an improved understanding of human health and disease on Earth.