Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA131837 | ENA |
REPOSITORIES: ENA
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Project description:Background: Staphylococcus aureus is a major pathogen of humans and animals and rapidly emerging antibiotic-resistant strains have further increased the severity of this health issue. Host genetics influence susceptibility to S. aureus infections, and genes determining infection outcome should be identified to analyze immune-based therapies as an alternative to antibiotics. Here, we used outbred animals from a divergent selection on susceptibility towards Staphylococcus infection to explore host immunogenetics. Methodology/Principal Findings: We investigated how dendritic cells respond to heat-inactivated S. aureus and whether dendritic cells from animals with different degree of susceptibility have distinct gene expression profiles. We measured expression levels of 15K probes from in vitro S. aureus-stimulated bone marrow-derived dendritic cells at three different time points (0, 3 and 8 hours) by using Agilent microarrays. Furthermore, a selected number of genes were confirmed by RT-qPCR. Gene signatures of stimulated DCs were obtained and genes involved in inflammatory process and T helper cell polarization were highly up regulated upon stimulation. Moreover, a set of 204 genes were statistically different between susceptible and resistant animals, and grouped them according to their predisposition to staphylococcal infection. Interestingly, a role of classical pathway of Complement and early regulation of inflammation is observed in the resistant line through over expression of C1q and Ido1 genes respectively. On the opposite, over expression of genes in the IL1R pathway in the susceptible animals was noticed. Furthermore, leucocyte extravasation pathway was also found dominant in the susceptible line. Conclusion/Significance: we successfully obtained Staphylococcus aureus associated gene expression of ovine BM-DC in 8 hour kinetics experiment. Distinct transcriptional profiles of dendritic cells obtained from resistant and susceptible lines may explain susceptibility towards S. aureus infections in a broad context. Keywords: Staphylococcus aureus, dendritic cells, mammalian, transcriptome, immunity, mastitis 44 sample records; two-colour dye-swap experimental design
2011-09-30 | E-GEOD-24448 | biostudies-arrayexpress
Project description:Background: Staphylococcus aureus is a major pathogen of humans and animals and rapidly emerging antibiotic-resistant strains have further increased the severity of this health issue. Host genetics influence susceptibility to S. aureus infections, and genes determining infection outcome should be identified to analyze immune-based therapies as an alternative to antibiotics. Here, we used outbred animals from a divergent selection on susceptibility towards Staphylococcus infection to explore host immunogenetics. Methodology/Principal Findings: We investigated how dendritic cells respond to heat-inactivated S. aureus and whether dendritic cells from animals with different degree of susceptibility have distinct gene expression profiles. We measured expression levels of 15K probes from in vitro S. aureus-stimulated bone marrow-derived dendritic cells at three different time points (0, 3 and 8 hours) by using Agilent microarrays. Furthermore, a selected number of genes were confirmed by RT-qPCR. Gene signatures of stimulated DCs were obtained and genes involved in inflammatory process and T helper cell polarization were highly up regulated upon stimulation. Moreover, a set of 204 genes were statistically different between susceptible and resistant animals, and grouped them according to their predisposition to staphylococcal infection. Interestingly, a role of classical pathway of Complement and early regulation of inflammation is observed in the resistant line through over expression of C1q and Ido1 genes respectively. On the opposite, over expression of genes in the IL1R pathway in the susceptible animals was noticed. Furthermore, leucocyte extravasation pathway was also found dominant in the susceptible line. Conclusion/Significance: we successfully obtained Staphylococcus aureus associated gene expression of ovine BM-DC in 8 hour kinetics experiment. Distinct transcriptional profiles of dendritic cells obtained from resistant and susceptible lines may explain susceptibility towards S. aureus infections in a broad context. Keywords: Staphylococcus aureus, dendritic cells, mammalian, transcriptome, immunity, mastitis
2011-10-01 | GSE24448 | GEO
Project description:Although it has recently been shown that A/J mice are highly susceptible to Staphylococcus aureus sepsis as compared to C57BL/6J, the specific genes responsible for this differential phenotype are unknown. Using chromosome substitution strains (CSS), we found that factors on chromosomes (chr) 8, 11, and 18 are responsible for susceptibility to S. aureus sepsis in A/J mice. F1 mice from C57BL/6J X CSS8 cross (C8A) and C57BL/6J X CSS18 (C18A) were also susceptible to S. aureus (median survival < 48 h), whereas F1 mice from C57BL/6J X CSS11 cross (C11A) were resistant (median survival > 120 h) to S. aureus. Bacterial loads in the kidney were consistent with F1 median survivals, with higher bacterial counts in susceptible mice. No sexlinked associations with susceptibility were noted in F1 intercrosses. Using whole genome transcription profiling, we identified a total of 192 genes on chromosomes 8, 11, and 18 which are differentially expressed between A/J and C57BL/6J in the setting of S. aureus infection. Of these, 28 genes had Gene Ontology annotations indicating a potential immune response function. These 28 genes are associated with susceptibility to S. aureus in A/J mice, and are potential determinants of susceptibility to S. aureus infection in humans. To identify genes for which differential expression between A/J and C57BL/6J mice could contribute to host susceptibility to S. aureus infection, we compared the gene expression profiles between uninfected A/J and C57BL/6J mice and between infected A/J and C57BL/6J mice at 2, 4, 6, and 12 hours after infection.
2010-08-01 | E-GEOD-19668 | biostudies-arrayexpress
Project description:Background: Staphylococcus aureus is a major pathogen of humans and animals. Host genetics influence the susceptibility to S. aureus infections, and genes determining infection outcome remain to be identified. Here, we used outbred animals from a divergent selection on susceptibility towards Staphylococcus infection to explore host immunogenetics. Methodology/Principal Findings: We investigated in vitro how mammary epithelial cells (MEC) respond to live S. aureus or S. aureus supernatant and whether MEC from animals with different degree of susceptibility to intra-mammary infections have distinct gene expression profiles. We measured the expression of 15K probes in MEC after each kind of stimulation (living bacteria or culture supernatant) at three different time points (a reference without bacteria, 1 and 5 hours) with ovine Agilent microarrays. Furthermore, a selected number of genes were confirmed by RT-qPCR. Gene signatures of stimulated MEC were obtained and genes involved in the cell cycle and metabolic processes were down-regulated during the kinetics and the apoptosis pathways were highly modified after both live bacteria and supernatant stimulations. Genes involved in immune response were up-regulated over-all after supernatant exposure. Furthermore 23 genes were differentially expressed between the resistant and susceptible animals, two of them were involed in oxidative processes, but the differences between the animals were very few. Conclusion/Significance: we successfully obtained Staphylococcus aureus associated gene expression of ovine MEC in a 5 hour kinetics experiment. The in vitro MEC model does not provide much information on the differences between Staphylococcus resistant and susceptible animals. Keywords: Staphylococcus aureus ; mammary epithelial cells ; mammalian ; transcriptome ; immunity ; mastitis 59 samples in a two-colour dye-swap experimental design.
2012-03-01 | E-GEOD-30390 | biostudies-arrayexpress
Project description:Although it has recently been shown that A/J mice are highly susceptible to Staphylococcus aureus sepsis as compared to C57BL/6J, the specific genes responsible for this differential phenotype are unknown. Using chromosome substitution strains (CSS), we found that factors on chromosomes (chr) 8, 11, and 18 are responsible for susceptibility to S. aureus sepsis in A/J mice. F1 mice from C57BL/6J X CSS8 cross (C8A) and C57BL/6J X CSS18 (C18A) were also susceptible to S. aureus (median survival < 48 h), whereas F1 mice from C57BL/6J X CSS11 cross (C11A) were resistant (median survival > 120 h) to S. aureus. Bacterial loads in the kidney were consistent with F1 median survivals, with higher bacterial counts in susceptible mice. No sexlinked associations with susceptibility were noted in F1 intercrosses. Using whole genome transcription profiling, we identified a total of 192 genes on chromosomes 8, 11, and 18 which are differentially expressed between A/J and C57BL/6J in the setting of S. aureus infection. Of these, 28 genes had Gene Ontology annotations indicating a potential immune response function. These 28 genes are associated with susceptibility to S. aureus in A/J mice, and are potential determinants of susceptibility to S. aureus infection in humans.
2010-08-01 | GSE19668 | GEO
Project description:Background: Staphylococcus aureus is a major pathogen of humans and animals. Host genetics influence the susceptibility to S. aureus infections, and genes determining infection outcome remain to be identified. Here, we used outbred animals from a divergent selection on susceptibility towards Staphylococcus infection to explore host immunogenetics. Methodology/Principal Findings: We investigated in vitro how mammary epithelial cells (MEC) respond to live S. aureus or S. aureus supernatant and whether MEC from animals with different degree of susceptibility to intra-mammary infections have distinct gene expression profiles. We measured the expression of 15K probes in MEC after each kind of stimulation (living bacteria or culture supernatant) at three different time points (a reference without bacteria, 1 and 5 hours) with ovine Agilent microarrays. Furthermore, a selected number of genes were confirmed by RT-qPCR. Gene signatures of stimulated MEC were obtained and genes involved in the cell cycle and metabolic processes were down-regulated during the kinetics and the apoptosis pathways were highly modified after both live bacteria and supernatant stimulations. Genes involved in immune response were up-regulated over-all after supernatant exposure. Furthermore 23 genes were differentially expressed between the resistant and susceptible animals, two of them were involed in oxidative processes, but the differences between the animals were very few. Conclusion/Significance: we successfully obtained Staphylococcus aureus associated gene expression of ovine MEC in a 5 hour kinetics experiment. The in vitro MEC model does not provide much information on the differences between Staphylococcus resistant and susceptible animals. Keywords: Staphylococcus aureus ; mammary epithelial cells ; mammalian ; transcriptome ; immunity ; mastitis
2012-03-01 | GSE30390 | GEO
Project description:It has been shown that inbred strains of mice exhibit variable susceptibility to S. aureus infection, but the specific genes responsible for this differential phenotype are unknown. Using ISHM to identify genomic regions associated with the phenotypes, we considered genes within those interval to be candidate genes and used the gene expression patterns of the genes contained in the region to determine whether the genes are differentially expressed between the 2 phenotypically different groups of mice. To identify genes differentially expressed between mice susceptible and resistant to S. aureus infection that could contribute to host susceptibility to S. aureus infection, we compared the gene expression profiles between 2 groups of mice where 3 were susceptible (A/J, BALBcBy/J, AKR/J) and resistant (C57BL/J, C3H/HeJ, NOD/ShiLtJ) to S. aureus. The susceptible group had high bacterial count values in the kidney while the resistant group had low values.
2011-12-31 | E-GEOD-23584 | biostudies-arrayexpress
Project description:Staphylococci are major pathogens in humans and animals and emerging antibiotic-resistant strains have further increased the importance of this health issue. The existence of a genetic basis of host response to bacterial infections has been widely documented but the underlying mechanisms and genes are still largely unknown. Previously, two divergent lines of sheep selected on their milk somatic cell count called high and low SCS lines, have been showed to be respectively more and less susceptible to intra mammary infections (IMI). Transcriptional profiling of milk somatic cells (MSC) of high and low SCS sheep infected successively by S. epidermidis and S. aureus was performed to provide enhanced knowledge about the genetic basis of differential host response to IMI with Staphylococci. Gene expression in MSC of high and low SCS sheep collected 12h post-challenge was performed on a 15K gene ovine oligoarray (Agilent). MSC were mainly neutrophils. The high number of differentially expressed genes between the two bacterial strains indicated, among others, increased number of T-cells in MSC after S. aureus, compared to S. epidermidis challenge. Differential regulation of 366 genes between resistant and susceptible animals was largely associated with immune and inflammatory response (including pathogen recognition TLR2 pathway and cell migration), signal transduction, cell proliferation and apoptosis. Close biological connection between most of differentially expressed genes into Ingenuity Pathway Analysis networks further indicated consistency between the genes that were differentially-expressed between resistant and susceptible animals. Gene profiling in high and low SCS sheep provided strong candidates for biological pathway and gene underlying genetically determined resistance and susceptibility towards Staphylococci infections opening new fields for further investigation. Keywords: Staphylococcus epidermidis, Staphylococcus aureus, milk somatic cells, mammalian, transcriptome, immunity, mastitis 22 samples in a two-colour dye-swap experimental design
2011-09-30 | E-GEOD-24925 | biostudies-arrayexpress
Project description:To unravel molecular targets involved in glycopeptide resistance, three isogenic strains of Staphylococcus aureus with different susceptibility levels to vancomycin or teicoplanin were subjected to whole-genome microarray-based transcription and quantitative proteomic profiling. Quantitative proteomics performed on membrane extracts showed exquisite inter-experimental reproducibility permitting the identification and relative quantification of >30% of the predicted S. aureus proteome. In the absence of antibiotic selection pressure, comparison of stable resistant and susceptible strains revealed 94 differentially expressed genes and 178 proteins. As expected, only partial correlation was obtained between transcriptomic and proteomic results during stationary-phase. Application of massively parallel methods identified one third of the complete proteome, a majority of which was only predicted based on genome sequencing, but never identified to date. Several over‑expressed genes represent previously reported targets, while series of genes and proteins possibly involved in the glycopeptide resistance mechanism were discovered here, including regulators, global regulator attenuator, hyper‑mutability factor or hypothetical proteins. Gene expression of these markers was confirmed in a collection of genetically unrelated strains showing altered susceptibility to glycopeptides. Our proteome and transcriptome analyses have been performed during stationary‑phase of growth on isogenic strains showing susceptibility or intermediate level of resistance against glycopeptides. Altered susceptibility had emerged spontaneously after infection with a sensitive parental strain, thus not selected in vitro. This combined analysis allows the identification of hundreds of proteins considered, so far as hypothetical protein. In addition, this study provides not only a global picture of transcription and expression adaptations during a complex antibiotic resistance mechanism but also unravels potential drug targets or markers that are constitutively expressed by resistant strains regardless of their genetic background, amenable to be used as diagnostic targets. Keywords: Molecular markers, antibiotic resistance, glycopeptides, growth-phase
2007-03-09 | GSE5188 | GEO
Project description:<p>In this study, we used admixture mapping to test the hypothesis that genomic variations with different frequencies in European and African ancestral genomes influence susceptibility to Staphylococcus aureus bacteremia (SAB) in a sample of African Americans. A total of 565 adult African Americans were genotyped for admixture mapping. Cases were unique African American adult inpatients with monomicrobial SAB (N=390) and controls are age-matched adult African American inpatients with no current or past S. aureus infection (N=175).</p> <p>After empirical multiplicity adjustment, one region on chromosome 6 (52 SNPs, P = 4.56e-05) in the HLA class II region was found to exhibit a genome-wide statistically significant increase in European ancestry. This region encodes genes involved in HLA-mediated immune response and these results provide additional evidence for genetic variation influencing HLA-mediated immunity, modulating susceptibility to SAB. </p>
| phs001441 | dbGaP