Integrated proteomic and transcriptomic analyses reveal the roles of Brucella BI-1 in cell division and membrane homeostasis of Brucella suis S2
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PROVIDER: PRJNA674828 | ENA |
REPOSITORIES: ENA
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Project description:To explore the role of Brucella BI-1 in Brucella suis S2, we constructed the Brucella BI-1 deletion mutant strain and its complementary strain. We then determined the effect of Brucella BI-1 deletion on the physiological characteristics of Brucella suis S2 and revealed them via integrated transcriptomic and proteomic analyses. Brucella BI-1 deletion altered the membrane properties of Brucella suis S2 and decreased its resistance to acidic pH, H2O2, polymyxin B, and lincomycin. Additionally, deleting Brucella BI-1 led to defective growth, cell division, and viability in Brucella suis S2. In conclusion, our results revealed that Brucella BI-1 is a bacterial cytoprotective protein involved in membrane homeostasis, cell division, and stress resistance in Brucella suis S2.
2021-02-17 | GSE160911 | GEO
Project description:To explore the role of Brucella BI-1 in Brucella suis S2, we constructed the Brucella BI-1 deletion mutant strain and its complementary strain. We then determined the effect of Brucella BI-1 deletion on the physiological characteristics of Brucella suis S2 and revealed them via integrated transcriptomic and proteomic analyses. Brucella BI-1 deletion altered the membrane properties of Brucella suis S2 and decreased its resistance to acidic pH, H2O2, polymyxin B, and lincomycin. Additionally, deleting Brucella BI-1 led to defective growth, cell division, and viability in Brucella suis S2. In conclusion, our results revealed that Brucella BI-1 is a bacterial cytoprotective protein involved in membrane homeostasis, cell division, and stress resistance in Brucella suis S2.
2020-11-13 | PXD022537 | iProX
Project description:Brucellosis is one of the most common zoonotic epidemics worldwide. Vaccination against Brucellosis is an important control strategy to prevent the disease in many high-prevalence regions. At present, Brucella vaccine strain S2 is the most widely used vaccine in China. In this study, to uncover the related mechanisms underlie virulence attenuation of S2, we characterized the transcriptional profile of S2 and 1330 infected macrophages by transcriptome analysis. The results revealed that expressions of 440 genes were significantly different between macrophages infected by 1330 and S2. Data analysis showed that in the gene ontology term, the different expressed genes involved in innate immune response, phagoctyosis, recognition, and inflammatory response were significantly enriched. Pathway enrichment analysis indicated that the genes involved in transcriptional misregulation in cancer, staphylococcus aureus infection pathways and NF-kappa B signaling pathway were significantly affected. To reveal the molecular mechanisms related to different expression profiles of infected macrophages, the transcription levels of the different genes between the two bacterial genomes were also detected. In total, the transcription of 29 different genes was significantly changed in either culture medium or infected microphages. The results of current study can be conducive to the promotion of better understanding of the related mechanisms underlie virulence attenuation of S2 and interactions between host cells and brucella strains.
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Project description:Brucellosis, caused by Brucella spp, is an important zoonotic disease leading to enormous economic losses in livestock and posing great threat to public health worldwide. The live attenuated Brucella suis (B. suis) strain S2 is a safe and effective vaccine, and it is most widely used in animals in China. However, S2 vaccination in animals may raise debates and concerns in terms of safety to primates, particularly human. In this study, using cynomolgus monkey as an animal model, we evaluated the safety of the S2 vaccine strain on primate, in addition, we performed transcriptome analysis to determine gene expression profiling on cynomolgus monkeys immunized with the S2 vaccine. Our results suggested that the S2 vaccine was safe to cynomolgus monkeys. Transcriptome analysis identified 663 differentially expressed genes (DEGs), of which 348 were significantly up-regulated and 315 were remarkably down-regulated. Gene Ontology (GO) classification and KEGG pathway analysis indicated that these DEGs were involved in various biological processes, including chemokine signaling pathway, actin cytoskeleton regulation, defense response, immune system processing, and type I interferon signaling pathway. The molecular functions of the DEGs mainly comprised of 2'-5'-oligoadenylate synthetase activity, double-stranded RNA binding and actin binding. Moreover, the cellular components of these DEGs included integrin complex, myosin II complex and blood microparticle. Our findings alleviate the concerns in safety of the S2 vaccine on primates and provide genetic basis of mammalian host response and gene regulation after vaccination with the S2 vaccine.
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Project description:Many pathogenic bacteria use a regulatory process termed Quorum Sensing (QS) to produce and detect small diffusible molecules to synchronize gene expression within a population. In Gram-negative bacteria, the detection and response to these molecules depend on transcriptional regulators belonging to the LuxR family. Such a system have been discovered in the intracellular pathogen Brucella melitensis, a Gram-negative bacteria responsible for brucellosis, a word-wide zoonosis remaining a serious public health concern in endemic countries. Two LuxR-type regulators, VjbR and BabR, have been identified in the genome of this pathogen. The vjbR mutant is highly attenuated in all tested models suggesting a crucial role of QS in the virulence of Brucella. This attenuation is at least due to the involvement of VjbR in the activation of the virB operon coding for a type four secretion system essential for Brucella to reach its intracellular replication compartment. At present, no function has been attributed to BabR. To assess the role of both Brucella QS-regulators, we performed in tandem comparative transcriptomic and proteomic analyses of vjbR and babR mutants. These experiments revealed that 10% of Brucella genome is regulated through those regulators, revealing that QS is a global regulatory system in this intracellular pathogen. The overlapping between BabR and VjbR targets suggest an unexpected cross-talk between these two regulators. Moreover, our results demonstrate that VjbR and BabR regulate many gene and/or proteins involved in stress response, metabolism and virulence. These targets are potentially involved in the adaptation of Brucella to the oxidative, pH and nutritional stresses encountered within the host. These findings highlight the involvement of QS in the virulence of Brucella and led us to suggest that this regulatory system could be implied in the spatial and sequential adaptation of Brucella to the host environment. Keywords: Quorum Sensing, Comparative gene expression, Brucella melitensis
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Project description:In order to uncover transcriptional changes occurring in Brucella- infected mouse brains that might lead to neurologic complications, we infected susceptible mice intranasally with Brucella and harvested their brains.
2023-03-17 | GSE217496 | GEO
Project description:Brucella spp. is an intracellular pathogen in vivo. The intracellular B. melitensis transcriptome was determined by initially enriched and then amplified B. melitensis RNA from total RNA of B. melitensis-infected HeLa cells. Analysis of microarray results identified 161 and 115 genes differentially expressed at 4 and 12 h p.i., respectively. Most of the genes (78%) differentially expressed were down-regulated at the earliest time point, but up-regulated (75%) at 12 h p.i. The analysis of the results indicates that Brucella undergo an adaptation period during the first 4 h p.i. that is overcome by 12 h p.i., permitting Brucella to replicate intracellularly. Specific genes and biological processes identified in this study will further help elucidate how Brucella act during the early infectious process to their eventual benefit and to the detriment of the naïve host. Keywords: Time course study of intracellular B. melitensis gene expression
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