Project description:Brucella abortus is an important zoonotic pathogen that causes severe economic loss to husbandry and poses a threat to human health. The B. abortus A19 live vaccine has been extensively used to prevent bovine brucellosis in China. However, A19 has the limitation of diagnosis interference and residual virulence for the host. In this study, a novel genetically marked vaccine, A19ΔvirB12, was generated and evaluated. The results indicated that A19ΔvirB12 was able to provide effective protection against B. abortus 2308 (S2308) challenge in mice and vaccinated sera can be distinguished from infected sera. However, previous studies have found that the accuracy of the serological detection method based on VirB12 protein needs to be improved. Therefore, we attempted to identify potential supplementary antigens with differential diagnosis function using label-free quantitative proteomics. Eighteen proteins identified only in S2308 were screened, and 7 of them were predicted to have high probability of antigenicity. In addition, 12 virulence factors were upregulated in S2308. The upregulation pathways of S2308 were significantly enriched in quorum sensing, ATP-binding cassette transporter, and metabolism. Several proteins related to cell division were significantly downregulated, while some proteins involved in transcription were upregulated in S2308.
Project description:Brucellosis is a critical zoonotic disease impacting humans and animals globally, causing symptoms like fever and arthritis in humans and reproductive issues in animals. The disease stems from the Brucella genus, adept at evading the immune system and proliferating within host cells. This study explores how Brucella abortus manipulates host cellular mechanisms to sustain infection, focusing on the interaction with murine macrophages over 24 hours. Initial host defenses involve innate immune responses, while Brucella's survival strategies include evading lysosomal degradation and modulating host cell functions through various pathways. The research identified significant transcriptional changes in macrophages post-infection, highlighting pathways such as cytokine storm, pyroptosis signaling, Toll-like receptor pathways and LXRs/RXRs signaling. The findings shed light on Brucella's complex mechanisms to undermine host defenses and underscore the need for further investigation into therapeutic targets to combat brucellosis.
Project description:In a time course study, we characterized global gene expression profile of B. abortus-infected macrophages from cattle naturally resistant (R) and susceptible (S) to brucellosis. B. abortus infection causes early down-regulation of transcript levels in Mø from R cattle at 4 h p.i. (22 up- and 126 down-regulated genes) which is reversed by 12 h post-infection (31 up- and 25 down-regulated genes), compared to uninfected control. On the other hand, B. abortus-infected S bovine macrophages exhibited a down-regulated expression profile at 4 (45 up- and 65 down-regulated genes) and 12 h p.i. (47 up- and 193 down-regulated genes). The analysis of the results indicates that B. abortus – infected Mø from cattle naturally R and S to brucellosis display different transcriptional profiles. Specific genes and biological processes identified in this study will further help elucidate how different macrophages from resistant and susceptible animals interact with Brucella during the early infectious process. Keywords: Expression profiling by microarray
Project description:Brucellosis is still a widespread zoonotic disease. Very little is known about the interaction between B. abortus and trophoblastic cells, which is essential for better understanding the pathogenesis of the Brucella-induced placentitis and abortion, a key event for transmission of the disease. The goal of this study was to evaluate the profile of gene expression by bovine trophoblastic cells during infection with B abortus. Explants of chorioallantoic membranes were inoculated with B. abortus strain 2308. Microarray analysis was performed at 4 h after infection, and expression of cytokines and chemokines by trophoblastic cells was assessed by real time RT-PCR at 6 and 12 h after inoculation. In addition, cytokine and chemokine expression was evaluated in placentomes from experimentally infected cows. Expression of pro-inflammatory genes by trophoblastic cells was suppressed at 4 h after inoculation, whereas a significant up-regulation of CXC chemokines, namely CXCL6 (GCP-2) and CXCL8 (IL-8), was observed at 12, but not at 6 h after inoculation. Placentomes of experimentally infected cows had a similar profile of chemokine expression, with upregulation of CXCL6 and CXCL8. Our data indicate that B. abortus modulates the innate immune response by trophoblastic cells, suppressing expression of pro-inflammatory mediators during the early stages of infection that is followed by a delayed and mild expression of pro-inflammatory chemokines, which is similar to the profile of chemokine expression in the placentomes of experimentally infected cows. This trophoblastic response is likely to contribute to the pathogenesis of B. abortus-induced placentitis. Keywords: trophoblast response to Brucella
Project description:The aim of this work is to unveil the gene regulatory networks - crucial for the different stages of intracellular survival - in the bovine and zoonotic pathogen Brucella abortus.These data are part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/