过度表达Pasteurella multocida OmpA诱导转录性变化及其对巨细胞两极分化可能的影响
Xiaohong Yang1, Qiaoyu Fu1, Wencan Zhang1
1Hainan Key Lab of Tropical Animal Reproduction, Breeding and Epidemic Disease Research, Animal Genetic Engineering Key Lab of Haikou, School of Animal Science and Technology, Hainan University, Haikou, Hainan, China.
Microbial pathogenesis
|June 23, 2023
概括
帕斯图雷拉多菌外膜蛋白A (OmpA) 改变免疫细胞基因表达,可能将巨细胞转移到类似M2的状态. 这项研究确定了参与P. multocida病变的关键途径和基因.
科学领域:
- 微生物学和免疫学
- 病原体与宿主之间的相互作用
- 基因组学和转录基因组学
背景情况:
- 帕斯托雷拉多 (P. multocida) 是一个重要的动物性传染病原体.
- 外膜蛋白A (OmpA) 是P. multocida的一个关键毒性因子,涉及生物膜形成,细胞感染和免疫调节.
- OmpA对宿主免疫反应的确切影响仍然不完全理解.
研究的目的:
- 通过检查其对免疫细胞转录组的影响,阐明P. multocida OmpA在病变发生中的作用.
- 调查OmpA如何影响大鼠膜巨细胞 (NR8383) 的基因表达特征.
主要方法:
- 通过lentiviral转导建立了一个稳定的OmpA过度表达细胞系 (NR8383).
- 在OmpA表达NR8383细胞上进行RNA测序 (Illumina HiSeq).
- 利用生物信息学分析,包括GO,KEGG,GSEA和PPI,以分析差异表达的基因和途径.
主要成果:
- 在对OmpA过度表达的反应中确定了1340个差异表达的基因.
- 显著改变的免疫相关途径包括焦点粘附,ECM受体相互作用,VEGF信号传递,抗原处理,NOD类和Toll类受体信号传递以及细胞因子-细胞因子受体相互作用.
- 已发现的关键基因包括Vegfa,Igf2r,Fabp5,P2rx1,C5ar1,Nedd4l,Gas6,Cxcl1,Pf4,Pdgfb,Thbs1,Col7a1,Vwf,Ccl9和Arg1.这些基因是最重要的基因.
结论:
- 在老鼠膜巨细胞中OmpA的表达导致了显著的转录基因变化.
- 观察到的途径和基因表达的变化表明OmpA可能会诱导巨细胞的表型转移到类似M2的状态.
- 鉴定的途径和基因为进一步研究P. multocida OmpA与宿主相互作用机制提供了基础.
相关概念视频
Transduction
Among the three main modes of HGT—transformation, conjugation, and transduction—transduction is unique in that it is mediated by bacteriophages, or bacterial viruses.Transduction occurs in two ways. Generalized transduction occurs during the lytic cycle of a bacteriophage infection. In this process, bacteriophages infect bacterial cells, replicate within them, and ultimately cause cell lysis, releasing newly assembled virions. Occasionally, random fragments of the bacterial genome are...
Determinants of Bacterial Pathogenicity and Virulence
Pathogenic bacteria employ a variety of strategies to establish infections, including the secretion of extracellular enzymes that act as potent virulence factors. These enzymes facilitate bacterial colonization of host tissues and help evade immune surveillance. By targeting structural components of host tissues and interfering with immune mechanisms, these enzymes play a pivotal role in disease progression.Extracellular Enzymes Facilitating Tissue Invasion: Several bacterial pathogens secrete...
Regulation of Bacterial Virulence
Pathogenic bacteria employ a range of regulatory mechanisms to modulate the expression of virulence genes in response to environmental and host-derived signals. These mechanisms ensure that virulence factors are expressed only under favorable conditions, thereby optimizing infection and survival strategies.Mechanisms of Virulence RegulationKey regulatory strategies include:Two-Component Systems: These consist of a membrane-bound sensor kinase and a cytoplasmic response regulator. Environmental...
Inhalation Anthrax
Anthrax is a zoonotic disease caused by Bacillus anthracis, a Gram-positive, spore-forming bacterium. It primarily affects herbivorous animals but can be transmitted to humans through skin contact, ingestion, or inhalation of spores.Cutaneous anthrax, the most common form, typically results from direct contact with bacterial spores through skin abrasions and is generally less severe. Gastrointestinal anthrax results from eating undercooked or contaminated meat. It affects the mouth, throat, or...
Atypical Pneumonia
Atypical pneumonia, often caused by Mycoplasma pneumoniae, is a form of pulmonary infection that differs from the classical presentation of bacterial pneumonia in both its cause and clinical symptoms. Mycoplasma pneumoniae is a pleomorphic bacterium notable for its lack of a rigid cell wall. This structural characteristic imparts resistance to beta-lactam antibiotics and significantly influences the bacterium’s behavior within the human host.Other pathogens responsible for the disease include...
Clinical Significance of Antibiotic Resistance
Methicillin-resistant Staphylococcus aureus (MRSA) presents a critical public health threat, arising from its capacity to resist β-lactam antibiotics due to acquisition of the mecA gene within the staphylococcal cassette chromosome mec (SCCmec). This gene encodes penicillin-binding protein 2a (PBP2a), which impairs binding efficacy of methicillin and other β-lactams. MRSA has evolved into distinct clonal lineages impacting humans and animals alike, reinforcing its significance within the One...


