Genetic diversity of Salmonella enterica during acute human infections

Abstract

The ubiquitous bacterial pathogen 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 infection diversity of acute salmonellosis using whole-genome sequencing of blood or stool isolates obtained from 23 different patients. We found that intestinal infections exhibited greater genetic variation than blood infections, including in their plasmid content. While same-patient isolates were separated by 10 single nucleotide polymorphisms or less, they often differed in the carriage of genes or alleles, including those associated with antibiotic resistance or virulence. Given the longstanding emphasis on single colony isolation in clinical and laboratory microbiology, these findings have implications for how we both study evolution and transmission and how we treat salmonellosis in an age of increasing antibiotic resistance.

Keywords: Salmonella enterica; infection diversity; whole genome sequencing.

Figure 1.

Phylogeny of 223 S. enterica human infection isolates. The interior-colored ring represents serovar information, the middle ring of light and dark gray indicates different patients, and the outer ring indicates isolate source, dark blue (stool) and dark red (blood).

Figure 2.

Same-patient variation in blood (red) and stool (blue) isolates. (a) SNP distances between same-patient isolate pairs. (b) Counts of breaks, duplications (dups), gaps, and jumps (relocation events) between same-patient isolate pairs. (c) Counts of plasmids per isolate. (d) Counts of changes in plasmid content between same-patient isolate pairs. (e) Pairwise SNP distances between S. Muenchen isolates from different patients (gray), and the same patient from blood or stool. *, p < 0.05; **, p < 0.01; ***, p < 0.001.

Figure 3.

Susceptibility testing of three same-patient isolates from two different patients with differential ARG predictions coincides with differential prediction of ARGs conferring aminoglycoside resistance.