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:Longitudinal analysis of Salmonella typhimurium mRNA from superspeader mouse cecal content and stool compared to in vitro Salmonella typhimurium mRNA.
Project description:Bacterial transcription factors (TFs) regulate gene expression to adapt to changing environments; when combined, the TF’s regulatory actions comprise transcriptional regulatory networks (TRNs). The chromatin immunoprecipitation (ChIP) assay is the major contemporary method for mapping in vivo protein-DNA interactions in the genome. It enables the genome-wide study of transcription factor binding sites (TFBSs) and gene regulation. Although rapidly accumulating publicly-available ChIP data are a valuable resource for the study of gene regulation, there are no full datasets of key regulators in Salmonella enterica Typhimurium LT2. Here, we present the genome-wide binding for YdcI in the Salmonella enterica Typhimurium LT2.
Project description:Investigation of whole genome gene expression level changes in a Salmonella enterica serovar Typhimurium UK1 delta-iacP mutant, compared to the wild-type strain. IacP is resoponsible for the secretion of virulence effector proteins via the type III secretion system, thereby contributing the virulence of S. Typhimurium. The mutants analyzed in this study are further described in Kim et al. 2011. Role of Salmonella Pathogenicity Island 1 Protein IacP in Salmonella enterica Serovar Typhimurium Pathogenesis. Infection and Immunity 79(4):1440-1450 (PMID 21263021).
Project description:To have a global picture of the miRNAs regulated upon Salmonella infection, we assessed small RNA changes, by RNA-sequencing, of HeLa cells infected with Salmonella Typhimurium compared with mock-treated cells . In addtion to the total population, we evaluated miRNA expression in the fraction of HeLa cells with internalized bacteria (Salmonella-positive), as well as in bystander cells, separated by fluorescence activated cell sorting (FACS)
Project description:RNA from in vitro grown Salmonella typhimurium is compared with RNA extracted from Salmonella typhimurium from infected chick caecums using a common DNA reference. Keywords: Disease state analysis, infected versus uninfected, common reference
Project description:Raghunathan2009 - Genome-scale metabolic
network of Salmonella typhimurium (iRR1083)
This model is described in the article:
Constraint-based analysis of
metabolic capacity of Salmonella typhimurium during
host-pathogen interaction.
Raghunathan A, Reed J, Shin S,
Palsson B, Daefler S.
BMC Syst Biol 2009; 3: 38
Abstract:
BACKGROUND: Infections with Salmonella cause significant
morbidity and mortality worldwide. Replication of Salmonella
typhimurium inside its host cell is a model system for studying
the pathogenesis of intracellular bacterial infections.
Genome-scale modeling of bacterial metabolic networks provides
a powerful tool to identify and analyze pathways required for
successful intracellular replication during host-pathogen
interaction. RESULTS: We have developed and validated a
genome-scale metabolic network of Salmonella typhimurium LT2
(iRR1083). This model accounts for 1,083 genes that encode
proteins catalyzing 1,087 unique metabolic and transport
reactions in the bacterium. We employed flux balance analysis
and in silico gene essentiality analysis to investigate growth
under a wide range of conditions that mimic in vitro and host
cell environments. Gene expression profiling of S. typhimurium
isolated from macrophage cell lines was used to constrain the
model to predict metabolic pathways that are likely to be
operational during infection. CONCLUSION: Our analysis suggests
that there is a robust minimal set of metabolic pathways that
is required for successful replication of Salmonella inside the
host cell. This model also serves as platform for the
integration of high-throughput data. Its computational power
allows identification of networked metabolic pathways and
generation of hypotheses about metabolism during infection,
which might be used for the rational design of novel
antibiotics or vaccine strains.
This model is hosted on
BioModels Database
and identified by:
MODEL1507180058.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
Project description:Investigation of whole genome gene expression level changes in a Salmonella enterica serovar Typhimurium 14028 delta GidA mutant The mutant described in this study is further analyzed in Shippy, D. C., N. M. Eakley, P. N. Bochsler, and A. A. Fadl. 2011. Biological and virulence characteristics of Salmonella enterica serovar Typhimurium following deletion of glucose-inhibited division (gidA) gene. Microb Pathog.
Project description:Investigation of whole genome gene expression level changes in Salmonella enterica serova Enteritidis and Typhimurium under chlorine treatment
Project description:LeuO, initially identified as a leucine regulator in Escherichia coli, has since been identified as a global regulator required for bacterial pathogenicity in a broad range of bacteria, including gram-negative pathogens, such as Salmonella, Shigella, and Vibrio; and gram-positive bacteria, such as Streptococcus pneumoniae. However, the regulatory roles and targets of LeuO vary among species. In the Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium), LeuO represses the transcription of Salmonella pathogenicity island (SPI)-1, thus diminishing the ability of the bacteria to invade host cells. However, its regulatory effect on SPI-2, essential for survival within macrophages, remains poorly understood. This study aimed to determine the regulatory role of LeuO in the intracellular persistence of S. Typhimurium. Overexpression of LeuO repressed the transcription of SPI-2 genes and accordingly decreased its protein levels. Chromatin immunoprecipitation sequencing revealed the genome-wide binding sites of LeuO in S. Typhimurium 14028 and identified a distinctive 23-nucleotide motif with high similarity to that previously discovered in E. coli. Notably, multiple LeuO-binding sites were predicted within SPI-2, primarily adjacent to the ssrA and ssrB loci. In vitro binding assays verified the high binding affinity between LeuO and three specific motifs located at positions -35 to -12 (ssrA1),+231 to +254 (ssrA2) near ssrA, and at positions -622 to -599 (ssrB3) near ssrB, relative to their transcription start sites. Furthermore, LeuO overexpression abolished the transcription of lacZ fused to the ssrA promoter containing ssrA1 and ssrA2, suggesting the direct repression of ssrA via LeuO-binding. The absence of LeuO increased the intracellular survival of S. Typhimurium within macrophages, whereas its overexpression attenuated bacterial persistence, which was presumably associated with the downregulation of SPI-2 by LeuO. This study reveals the versatile regulatory mechanisms of LeuO and underscores its pivotal role in modulating SPI-2 expression, thereby providing key insights into the fine tuning of virulence by Salmonella during systemic infection.