Genome wide host gene expression analysis in Mice infected with Pasteurella multocida
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE83502 | GEO | 2017/01/01
SECONDARY ACCESSION(S): PRJNA326199
REPOSITORIES: GEO
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Project description:Pasteurella multocida causes acute septicemic and respiratory diseases, including haemorrhagic septicaemia, in cattle and buffalo with case fatality of 100%. In the present study, mice were infected with P. multocida (1.6 × 103 cfu, intraperitoneal) to evaluate host gene expression profile at early and late stages of infection using high throughput microarray transcriptome analyses. Several differentially expressed genes (DEGs) at both the time points were identified in P.multocida infected spleen, liver and lungs. Functional annotation of these DEGs showed enrichment of key pathways such as TLR, NF-κB, MAPK, TNF, JAK-STAT and NOD like receptor signaling pathways. Several DEGs overlapped across different KEGG pathways indicating a crosstalk between them. The predicted protein-protein interaction among these DEGs suggested, that the recognition of P. multocida LPS or outer membrane components by TLR4 and CD14, results in intracellular signaling via MyD88, IRAKs and/or TRAF6 leading to activation of NFκB and MAPK pathways and associated cytokines.
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Project description:The mitogenic dermonecrotic toxin from Pasteurella multocida (PMT) is a 1285-residue multipartite protein that belongs to the A-B family of bacterial protein toxins. Through its G-protein-deamidating activity on the α subunits of heterotrimeric G(q)-, G(i)- and G(12/13)-proteins, PMT potently stimulates downstream mitogenic, calcium, and cytoskeletal signaling pathways. These activities lead to pleiotropic effects in different cell types, which ultimately result in cellular proliferation, while inhibiting cellular differentiation, and account for the myriad of physiological outcomes observed during infection with toxinogenic strains of P. multocida.
| S-EPMC4408768 | biostudies-literature
Project description:Pasteurella multocida is a highly versatile pathogen capable of causing infections in a wide range of domestic and wild animals as well as in humans and nonhuman primates. Despite over 135 years of research, the molecular basis for the myriad manifestations of P. multocida pathogenesis and the determinants of P. multocida phylogeny remain poorly defined. The current availability of multiple P. multocida genome sequences now makes it possible to delve into the underlying genetic mechanisms of P. multocida fitness and virulence. Using whole-genome sequences, the genotypes, including the capsular genotypes, lipopolysaccharide (LPS) genotypes, and multilocus sequence types, as well as virulence factor-encoding genes of P. multocida isolates from different clinical presentations can be characterized rapidly and accurately. Putative genetic factors that contribute to virulence, fitness, host specificity, and disease predilection can also be identified through comparative genome analysis of different P. multocida isolates. However, although some knowledge about genotypes, fitness, and pathogenesis has been gained from the recent whole-genome sequencing and comparative analysis studies of P. multocida, there is still a long way to go before we fully understand the pathogenic mechanisms of this important zoonotic pathogen. The quality of several available genome sequences is low, as they are assemblies with relatively low coverage, and genomes of P. multocida isolates from some uncommon host species are still limited or lacking. Here, we review recent advances, as well as continuing knowledge gaps, in our understanding of determinants contributing to virulence, fitness, host specificity, disease predilection, and phylogeny of P. multocida.
| S-EPMC6759666 | biostudies-literature
Project description:Objectives: To determine the transcripts that are differentially expressed in a hfq mutant. Hfq is an RNA chaperone that mediates many interactions between regultory RNAs and their mRNA targets. Analysis of the transcriptomes of the Pasteurella multocida wild-type strain and the Pasteurella multocida hfq mutant will allow for identification of genes controlled by hfq and the sRNAs with which it interacts.
2016-03-02 | GSE77721 | GEO
Project description:The Gram-negative pathogen Pasteurella multocida is responsible for many important animal diseases. While a number of P. multocida virulence factors have been identified, very little is known about how gene expression and protein production is regulated in this organism. One mechanism by which bacteria regulate transcript abundance and protein production is riboregulation, which involves the interaction of a small RNA (sRNA) with a target mRNA to alter transcript stability and/or translational efficiency. This interaction often requires stabilization by a ribosome binding protein such as ProQ or Hfq. In E. coli and other species, ProQ has been shown to play a critical role in stabilizing sRNA-mRNA interactions and preferentially binds to 3’ stem-loop regions of the mRNA transcripts, characteristic of intrinsic transcriptional terminators. The aim of this study was to determine the role of ProQ riboregulation in P. multocida and identify the RNA regions to which it binds. We assessed differentially expressed transcripts in a proQ mutant and identified sites of direct ProQ-RNA interaction using in vivo UV-crosslinking and analysis of cDNA (CRAC). These analyses demonstrated that ProQ binds to, and stabilises, ProQ-dependant sRNAs and transfer RNAs in P. multocida via adenosine enriched, highly structured sequences. The binding of ProQ to two RNA molecules was characterised and showed that ProQ bound within the coding sequence of the uncharacterized PmVP161_1121 and within the 3’ region of the sRNA Prrc13.
2022-03-02 | GSE196834 | GEO
Project description:Objectives: To determine the transcripts that are differentially expressed in a hfq mutant. Hfq is an RNA chaperone that mediates many interactions between regultory RNAs and their mRNA targets. Analysis of the transcriptomes of the Pasteurella multocida wild-type strain and the Pasteurella multocida hfq mutant will allow for identification of genes controlled by hfq and the sRNAs with which it interacts. Methods: RNA sequencing was employed to determine the transcriptomes of a wild-type Pasteurella multocida strain and a hfq mutant strain. Comparison of these two transcriptomes allows for determination of differentially expressed genes and therefore those genes controlled by Hfq and sRNAs with which it interacts.
2016-03-02 | E-GEOD-77721 | biostudies-arrayexpress
Project description:BackgroundBacteriophages play important roles in the evolution of bacteria and in the emergence of new pathogenic strains by mediating the horizontal transfer of virulence genes. Pasteurella multocida is responsible for different disease syndromes in a wide range of domesticated animal species. However, very little is known about the influence of bacteriophages on disease pathogenesis in this species.ResultsTemperate bacteriophage diversity was assessed in 47 P. multocida isolates of avian (9), bovine (8), ovine (10) and porcine (20) origin. Induction of phage particles with mitomycin C identified a diverse range of morphological types representing both Siphoviridae and Myoviridae family-types in 29 isolates. Phage of both morphological types were identified in three isolates indicating that a single bacterial host may harbour multiple prophages. DNA was isolated from bacteriophages recovered from 18 P. multocida isolates and its characterization by restriction endonuclease (RE) analysis identified 10 different RE types. Phage of identical RE types were identified in certain closely-related strains but phage having different RE types were present in other closely-related isolates suggesting possible recent acquisition. The host range of the induced phage particles was explored using plaque assay but only 11 (38%) phage lysates produced signs of infection in a panel of indicator strains comprising all 47 isolates. Notably, the majority (9/11) of phage lysates which caused infection originated from two groups of phylogenetically unrelated ovine and porcine strains that uniquely possessed the toxA gene.ConclusionsPasteurella multocida possesses a wide range of Siphoviridae- and Myoviridae-type bacteriophages which likely play key roles in the evolution and virulence of this pathogen.
| S-EPMC8008546 | biostudies-literature
Project description:Pasteurella multocida is a leading cause of respiratory diseases in many host species. To understand the genetic characteristics of P. multocida strains isolated from different host species, we sequenced the genomic DNA of P. multocida isolated from pigs and analyzed the genetic characteristics of strains from avian species, bovine species, pigs, and rabbits using whole genome sequence (WGS) data. Our results found that a capsular: lipopolysaccharide (LPS): multilocus sequence typing (MLST) genotype A: L1: ST129 (43.75%) was predominant in avian P. multocida; while genotypes B: L2: ST122 (60.00%) and A: L3: ST79 (30.00%) were predominate in bovine P. multocida; genotype D: L6: ST50 (37.50%) in porcine P. multocida; and genotype A: L3: ST9 (76.47%) in rabbit P. multocida. Comparative genomic analysis of P. multocida from different host species found that there are no genes in the P. multocida genome that are specific to any type of host. Phylogenetic analysis using either whole-genome single nucleotide polymorphisms (SNPs) or the set of SNPs present in all single-copy core genes across genomes showed that P. multocida strains with the same LPS genotype and MLST genotype were clustered together, suggesting the combining both the LPS and MLST typing schemes better explained the topology seen in the P. multocida phylogeny.
| S-EPMC6029419 | biostudies-literature
Project description:Pasteurella multocida can cause goat hemorrhagic sepsis and endemic pneumonia. Respiratory epithelial cells are the first line of defense in the lungs during P. multocida infection. These cells act as a mechanical barrier and activate immune response to protect against invading pathogenic microorganisms. Upon infection, P. multocida adheres to the cells and causes changes in cell morphology and transcriptome. ATAC-seq was conducted to determine the changes in the chromatin open region of P. multocida-infected goat bronchial epithelial cells based on transcriptional regulation. A total of 13,079 and 28,722 peaks were identified in the control (CK) and treatment (T) groups (P. multocida infection group), respectively. The peaks significantly increased after P. multocida infection. The specific peaks for the CK and T groups were annotated to 545 and 6632 genes, respectively. KEGG pathway enrichment analysis revealed that the specific peak-related genes in the T group were enriched in immune reaction-related pathways, such as Fc gamma R-mediated phagocytosis, MAPK signaling pathway, bacterial invasion of epithelial cells, endocytosis, and autophagy pathways. Other cellular component pathways were also enriched, including the regulation of actin cytoskeleton, adherent junction, tight junction, and focal adhesion. The differential peaks between the two groups were subsequently analyzed. Compared to those in the CK group, 863 and 11 peaks were upregulated and downregulated, respectively, after the P. multocida infection. Fifty-six known transcription factor motifs were revealed in upregulated peaks in the P. multocida-infected group. By integrating ATAC-seq and RNA-seq, some candidate genes (SETBP1, RASGEF1B, CREB5, IRF5, TNF, CD70) that might be involved in the goat bronchial epithelial cell immune reaction to P. multocida infection were identified. Overall, P. multocida infection changed the structure of the cell and caused chromatin open regions to be upregulated. In addition, P. multocida infection actively mobilized the host immune response with the inflammatory phenotype. The findings provide valuable information for understanding the regulatory mechanisms of P. multocida-infected goat bronchial epithelial cells.
| S-EPMC9861026 | biostudies-literature
Project description:Quantitative proteomics comparison wt and Hfq mutant Pasteurella multocida strains.
2016-03-14 | PXD003586 | Pride