Salmonella enterica Raw sequence reads
Salmonella enterica is the causative agent of both enteric fever and gastroenteritis. Despite its significant global health burden, we lack an understanding of its genetic diversity during acute infection, with ramifications for treatment and prevention. Here, we investigated within-host diversity of acute infections using whole-genome sequencing of isolates from the blood or stool of 23 patients. While same-patient isolates were always the same serovar, and separated by 10 single nucleotide polymorphisms (SNPs) or less, they often differed in the carriage or genes or alleles associated with antibiotic resistance or virulence. Stool isolates exhibited greater variation than blood isolates, including in their plasmid content, possibly due to exposure to diverse mobile genetic elements in the gut, and/or bottlenecking during the transition from gut to bloodstream. Given the longstanding emphasis on single colony isolation in clinical microbiology, these findings have important implications both for how we study evolution and transmission, but also for treatment of this important pathogen in an age of increasing antibiotic resistance.