Transposon mutagenesis reveals differential essential pathways in model Salmonella Typhimurium strains SL1344 and SL3261

Salmonella enterica is a globally disseminated pathogen that is the cause of over 100 million infections per year. The resulting diseases caused by S. enterica are dependent upon host susceptibility and the infecting serovar. For example, Typhoid fever is a human exclusive disease caused by S. enterica serovar Typhi. As S. enterica serovar Typhimurium induces a typhoid like disease in mice, this model has been used extensively to illuminate various aspects of Salmonella infection and host responses. However, the infection is so severe that even one infectious bacterium injected intravenously will cause mortality in 100% of animals within one week of infection. Due to this severity, researchers often use strains of mice resistant to infection or attenuated Salmonella strains to understand adaptive immunity and infection dynamics. Despite decades of research, many aspects of Salmonella infection and fundamental biology remain poorly understood. Here, we use a Transposon Insertion Sequencing (TIS) technique to interrogate the essential genomes of widely used isogenic wild-type and attenuated S. Typhimurium strains. We reveal differential essential pathways between strains, provide a direct link between iron starvation, DNA synthesis and bacterial membrane integrity, and show S. Typhi and S. Typhimurium have similar requirements for iron