Overexpression of Pasteurella multocida OmpA induces transcriptional changes and its possible implications for the macrophage polarization

Yang, XIAO-Hong; Fu, Qiaoyu; Zhang, Wencan; An, Qi; Zhang, Zhenxing; Li, Hong; Chen, Xiangying; Chen, Zhe; Cheng, Yuda; Chen, Si; Man, Churiga; Du, Lijun; Chen, Qiaoling; Wang, Fengyang

doi:10.1016/j.micpath.2023.106212

Cited by 3 publications

(2 citation statements)

References 37 publications

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“…Focal adhesions are composed of several proteins, among which integrins, dimers composed of an alpha subunit and a beta subunit, are the main cell adhesion receptors [ 35 ]. A recent study also suggested that the key virulence protein of P. multocida , OmpA, has an impact on focal adhesion [ 55 ]. In the present study, we found that the expression of integrin α proteins and the downstream effector p-Fak decreased in vivo after P. multocida infection, suggesting that P. multocida inhibited focal adhesion.…”

Section: Discussionmentioning

confidence: 99%

Pasteurella multocida activates apoptosis via the FAK-AKT-FOXO1 axis to cause pulmonary integrity loss, bacteremia, and eventually a cytokine storm

Zhao,

Tang,

Dan

et al. 2024

Vet Res

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Pasteurella multocida is an important zoonotic respiratory pathogen capable of infecting a diverse range of hosts, including humans, farm animals, and wild animals. However, the precise mechanisms by which P. multocida compromises the pulmonary integrity of mammals and subsequently induces systemic infection remain largely unexplored. In this study, based on mouse and rabbit models, we found that P. multocida causes not only lung damage but also bacteremia due to the loss of lung integrity. Furthermore, we demonstrated that bacteremia is an important aspect of P. multocida pathogenesis, as evidenced by the observed multiorgan damage and systemic inflammation, and ultimately found that this systemic infection leads to a cytokine storm that can be mitigated by IL-6-neutralizing antibodies. As a result, we divided the pathogenesis of P. multocida into two phases: the pulmonary infection phase and the systemic infection phase. Based on unbiased RNA-seq data, we discovered that P. multocida-induced apoptosis leads to the loss of pulmonary epithelial integrity. These findings have been validated in both TC-1 murine lung epithelial cells and the lungs of model mice. Conversely, the administration of Ac-DEVD-CHO, an apoptosis inhibitor, effectively restored pulmonary epithelial integrity, significantly mitigated lung damage, inhibited bacteremia, attenuated the cytokine storm, and reduced mortality in mouse models. At the molecular level, we demonstrated that the FAK-AKT-FOXO1 axis is involved in P. multocida-induced lung epithelial cell apoptosis in both cells and animals. Thus, our research provides crucial information with regard to the pathogenesis of P. multocida as well as potential treatment options for this and other respiratory bacterial diseases.

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Section: Discussionmentioning

confidence: 99%

Pasteurella multocida activates apoptosis via the FAK-AKT-FOXO1 axis to cause pulmonary integrity loss, bacteremia, and eventually a cytokine storm

Zhao,

Tang,

Dan

et al. 2024

Vet Res

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“…Alfano et al have proposed that it is important to understand the roles of extracellular matrix (ECM) and microbiota in the development and progression of urothelial carcinomas 34 . For example, the outer membrane protein A of Pasteurella multocida induces changes in the transcriptome of alveolar macrophages, which are associated with the ECM 35 . Pseudomonas aeruginosa can infiltrate the ECM by secreting alkaline proteases under anaerobic conditions in vitro (e.g., tumor tissue) 34 .…”

Section: Discussionmentioning

confidence: 99%

Uncovering Microbial Composition of the Tissue Microenvironment in Bladder Cancer using RNA Sequencing Data

Yao,

Ai,

Wang

et al. 2024

J. Cancer

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Purpose: Bladder cancer (BC) is one of the top 10 common tumors in the world. It has been reported that microbiota can colonize tissues and play important roles in tumorigenesis and progression. However, the current understanding of microorganisms in the BC tissue microenvironment remains unclear. Methods: In this study, we integrated the RNA-seq data of 479 BC tissue samples from seven datasets combined with a range of bioinformatics tools to explore the landscape of microbiome in the BC tissue microenvironment. Results: The pan-microbiome was estimated to surpass 1,400 genera. A total of seven core microbiota ( Bacillus , Corynebacterium , Cutibacterium , Escherichia , Halomonas , Pasteurella , and Streptomyces ) were identified. Among them, Bacillus was widely distributed in all datasets with a high relative abundance (10.11% of all samples on average). Moreover, some biological factors, including tissue source and tumor grade, were found significant effects on the microbial composition of the bladder tissue. Pseudomonas , Porphyrobacter , and Acinetobacter were enriched in tumor tissues, while Mycolicibacterium and Streptomyces were enriched in patients who showed durable response to BCG therapy. In addition, we established microbial co-occurrence networks and found that the BCG therapy may attenuate the microbiological interactions. Conclusions: This study clearly provided a microbial landscape of the BC tissue microenvironment, which was important for exploring the interactions between microorganisms and BC tissues. The identified specific taxa might be potential biomarkers for BC.

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Characterization and immunological effect of outer membrane vesicles from Pasteurella multocida on macrophages

Sun,

Huang,

et al. 2024

Appl Microbiol Biotechnol

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Pasteurella multocida is an important bacterial pathogen that can cause diseases in both animals and humans. Its elevated morbidity and mortality rates in animals result in substantial economic repercussions within the livestock industry. The prevention of diseases caused by P. multocida through immunization is impeded by the absence of a safe and effective vaccine. Outer membrane vesicles (OMVs) secreted from the outer membrane of Gram-negative bacteria are spherical vesicular structures that encompass an array of periplasmic components in conjunction with a diverse assortment of lipids and proteins. These vesicles can induce antibacterial immune responses within the host. P. multocida has been shown to produce OMVs. Nonetheless, the precise characteristics and immunomodulatory functions of P. multocida OMVs have not been fully elucidated. In this study, OMVs were isolated from P. multocida using an ultrafiltration concentration technique, and their morphology, protein constitution, and immunomodulatory properties in RAW264.7 cells were studied. Transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) revealed that the OMVs exhibited typical spherical and bilayered lipid vesicular architecture, exhibiting an average diameter of approximately 147.5 nm. The yield of OMVs was 2.6 × 1011 particles/mL. Proteomic analysis revealed a high abundance of membrane-associated proteins within P. multocida OMVs, with the capability to instigate the host’s immune response. Furthermore, OMVs stimulated the proliferation and cellular uptake of macrophages and triggered the secretion of cytokines, such as TNF-ɑ, IL-1β, IL-6, IL-10, and TGF-β1. Consequently, our results indicated that OMVs from P. multocida could directly interact with macrophages and regulate their immune function in vitro. These results supported the prospective applicability of P. multocida OMVs as a platform in the context of vaccine development. Key points • Preparation and characterization of P. multocida OMVs. • P. multocida OMVs possess a range of antigens and lipoproteins associated with the activation of the immune system. • P. multocida OMVs can activate the proliferation, internalization, and cytokine secretion of macrophages in vitro.

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Overexpression of Pasteurella multocida OmpA induces transcriptional changes and its possible implications for the macrophage polarization

Cited by 3 publications

References 37 publications

Pasteurella multocida activates apoptosis via the FAK-AKT-FOXO1 axis to cause pulmonary integrity loss, bacteremia, and eventually a cytokine storm

Pasteurella multocida activates apoptosis via the FAK-AKT-FOXO1 axis to cause pulmonary integrity loss, bacteremia, and eventually a cytokine storm

Uncovering Microbial Composition of the Tissue Microenvironment in Bladder Cancer using RNA Sequencing Data

Characterization and immunological effect of outer membrane vesicles from Pasteurella multocida on macrophages

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