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High-throughput Fitness Experiments Reveal Specific Vulnerabilities of Human-Adapted Salmonella During Stress and Infection- Barseq13 (Typhi and Paratyphi A infection of THP-1 human macrophages)

ABSTRACT: Salmonella enterica is comprised of genetically distinct “serovars”, that together provide an intriguing model for exploring the genetic basis of pathogen evolution. While the genomes of numerous Salmonella isolates with broad variations in host range and human disease manifestations have been sequenced, the functional links between genetic and phenotypic differences among these serovars remain poorly understood. Here, we conduct high-throughput functional genomics on both generalist (Typhimurium) and human-restricted (Typhi & Paratyphi A) Salmonella at unprecedented scale in the study of this enteric pathogen. Using a comprehensive systems biology approach, we identify gene networks with serovar-specific fitness effects across 25 host-associated stresses encountered at key stages of human infection. By experimentally perturbing these networks, we characterize previously undescribed pseudogenes in human-adapted Salmonella. Overall, this work highlights specific vulnerabilities encoded within human-restricted Salmonella that are linked to the degradation of their genomes, shedding light into the evolution of this enteric pathogen.

ORGANISM(S): Salmonella enterica subsp. enterica serovar Paratyphi A str. ATCC 9150 Salmonella enterica subsp. enterica serovar Typhi str. Ty2

PROVIDER: GSE262769 | GEO | 2024/04/12

REPOSITORIES: GEO

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