Project description:Salmonella enterica serovar Typhimurium (S. Typhimurium) definitive phage type 104 (DT104) has caused significant morbidity and mortality in humans and animals for almost three decades. We have completed the full DNA sequence of one DT104 strain, NCTC13348 and show that the main differences between the genome of this isolate and the previously sequenced S. Typhimurium LT2 lie in integrated prophage elements and the Salmonella Genomic Island 1 encoding antibiotic resistance genes. Thirteen isolates of S. Typhimurium DT104 with different pulsed field gel electrophoresis (PFGE) profiles were analyzed by multi locus sequence typing (MLST), plasmid profiling, hybridization to a Pan-Salmonella DNA microarray and prophage-based multiplex PCR. All the isolates belonged to a single MLST type ST19. Microarray data demonstrated that the 13 DT104 isolates were remarkably conserved in gene content. The PFGE band-size differences in these isolates could be explained to a great extent by changes in prophage and plasmid content. Thus, here the nature of variation in different S. Typhimurium DT104 isolates is further defined at the genome level illustrating how this phage type is evolving over time.
Project description:A collection of 61 Salmonella enterica serovar Typhimurium (S. Typhimurium) of animal and human origin, matched as closely as possible by phage type, antimicrobial resistance pattern and place / time of isolation, and sourced from farms or hospitals in Scotland, were analysed by antimicrobial susceptibility testing, phage typing, pulsed field gel electrophoresis (PFGE), plasmid profiling and DNA microarrays. PFGE of all 61 isolates revealed ten PFGE profiles, which clustered by phage type and antibiotic resistance pattern, with human and animal isolates distributed between PFGE profiles. Analysis of 23 representative S. Typhimurium strains hybridised to a composite Salmonella DNA microarray identified a small number of specific regions of genome variation between different phage types and PFGE profiles. These variable regions of DNA were typically located within prophage-like elements. Simple PCR assays were subsequently designed to discriminate between different isolates from the same geographical region.
Project description: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.
Project description: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.
Project description: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.
Project description: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.
Project description: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.
Project description: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.
Project description: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.
Project description: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.