Persistent Salmonella infections in humans are associated with mutations in the BarA/SirA regulatory pathway

Grote, Alexandra; Piscon, Bar; Manson, Abigail L.; Adani, Boaz; Cohen, Helit; Livny, Jonathan; Earl, Ashlee M.; Gal-Mor, Ohad

doi:10.1016/j.chom.2023.12.001

Cited by 3 publications

(1 citation statement)

References 86 publications

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“…Intriguingly, mutations in barA and sirA exhibited increased fitness under multiple stresses (Supplementary Fig. 8f ), possibly explaining their frequent occurrence in chronically infected Salmonella patients 51 .…”

Section: Resultsmentioning

confidence: 98%

High-throughput fitness experiments reveal specific vulnerabilities of human-adapted Salmonella during stress and infection

Wang,

Leshchiner,

Luo

et al. 2024

Nat Genet

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Salmonella enterica is comprised of genetically distinct ‘serovars’ that together provide an intriguing model for exploring the genetic basis of pathogen evolution. Although 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 and 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.

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Section: Resultsmentioning

confidence: 98%

High-throughput fitness experiments reveal specific vulnerabilities of human-adapted Salmonella during stress and infection

Wang,

Leshchiner,

Luo

et al. 2024

Nat Genet

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Contamination Status and Serotypes Distribution of Salmonella in Food in Yantai City, China: A 14-Year Continuous Monitoring Study

Dong,

Wang,

Feng

et al. 2024

Foodborne Pathogens and Disease

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A genome-wide collection of barcoded single-gene deletion mutants in Salmonella enterica serovar Typhimurium

Porwollik,

Chu,

Desai

et al. 2024

PLoS ONE

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Genetic screening of pools of mutants can reveal genetic determinants involved in complex biological interactions, processes, and systems. We previously constructed two single-gene deletion resources for Salmonella enterica serovar Typhimurium 14028s in which kanamycin (KanR) and chloramphenicol (CamR) cassettes were used to replace non-essential genes. We have now used lambda-red recombination to convert the antibiotic cassettes in these resources into a tetracycline-resistant (TetR) version where each mutant contains a different 21-base barcode flanked by Illumina Read1 and Read2 primer sequences. A motility assay of a pool of the entire library, followed by a single-tube processing of the bacterial pellet, PCR, and sequencing, was used to verify the performance of the barcoded TetR collection. The new resource is useful for experiments with defined subsets of barcoded mutant strains where biological bottlenecks preclude high numbers of founder bacteria, such as in animal infections. The TetR version of the library will also facilitate the construction of triple mutants by transduction. The resource of 6197 mutants covering 3490 genes is deposited at Biological and Emerging Infections Resources (beiresources.org).

show abstract

Persistent Salmonella infections in humans are associated with mutations in the BarA/SirA regulatory pathway

Cited by 3 publications

References 86 publications

High-throughput fitness experiments reveal specific vulnerabilities of human-adapted Salmonella during stress and infection

High-throughput fitness experiments reveal specific vulnerabilities of human-adapted Salmonella during stress and infection

Contamination Status and Serotypes Distribution of Salmonella in Food in Yantai City, China: A 14-Year Continuous Monitoring Study

A genome-wide collection of barcoded single-gene deletion mutants in Salmonella enterica serovar Typhimurium

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