Investigation of evolutionary dynamics and genetic heterogeneity of Salmonella in persistent bacteremia

Persistent and recurrent Salmonella bacteremia remains a significant clinical challenge associated with high morbidity. The pathogen's ability to adapt within the host often leads to recurrent infections, necessitating in-depth analysis to determine if genetic heterogeneity drives this persistence. This study employs whole genome sequencing and strain phasing to investigate the evolutionary dynamics and intra-host genetic landscape of Salmonella populations in patients with persistent or recurrent bloodstream infections.

By analyzing 31 isolates from 14 patients, we used whole genome sequencing, coupled with comprehensive bioinformatics analysis, including single nucleotide polymorphisms identification, strain phasing, and phylogenetic analysis, to explore genetic heterogeneity and evolutionary patterns.

A total of four Salmonella serotypes were identified, including S. enterica serovar Typhimurium, Typhi, Schwarzengrund, and Enteritidis, with Enteritidis being the most prevalent. Our findings revealed genetic heterogeneity shift at colony level between early and later same-patient isolates. We discovered several missense mutations in genes such as rcsB, yjiK, dsbA, glyQ and gltB, with changes in their proportions between early and later same-patient isolates. These genes are implicated in key bacterial adaptation strategies, including modulation of virulence, membrane permeability, and antibiotic resistance.

Our research sheds light on the complex genetic landscape of Salmonella in persistent and recurrent bacteremia, highlighting the potential contribution of specific genetic mutations in the pathogen's survival and adaptability. These insights not only contribute to our understanding of Salmonella pathogenesis, but also underscore the potential for developing targeted therapeutic interventions to address the challenges posed by persistent infections.