Glaesserella parasuis can cause serious systemic disease (Glasser’s disease) that is characterized by fibrinous polyserositis, polyarthritis and meningitis. cAMP receptor protein (CRP) is among the well studied global regulator proteins which could modulate the virulence of many pathogenic bacteria. Our previous study showed that the crp gene was involved in the regulation of growth rate, biofilm formation, stress tolerance, serum resistance, and iron utilization in G. parasuis. However, whether the crp gene could regulate the virulence of G. parasuis has not been analyzed previously. In this study, it was observed that the crp gene in G. parasuis serovar 5 (HPS5) was involved in regulating the adhesion and invasion abilities on iPAM cells, and the mRNA expression of various virulence-related factors. It also possessed the ability to induce the mRNA expression of pro-inflammatory cytokines (IL-1α, IL-1β, IL-6, IL-8 and TNF-α), promoted the activation of the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways in porcine kidney epithelial (PK-15) and immortalized swine pulmonary alveolar macrophage (iPAM) cells, and contributed to the pathogenicity and organs colonization in mice. As compared with the wild type, both the expression of virulence-related factors in the crp mutant strain and its ability to induce the mRNA expression of pro-inflammatory cytokines, as well as the expression of phospho-p65 and phospho-p38 in PK-15 and iPAM cells was reduced significantly. Furthermore, it also found that the virulence of crp mutant was significantly reduced as compared with the wild type. However, the abilities of adherence and invasion on iPAM cell of Δcrp strain was noted to be significantly enhanced as compared with the wild type. These results suggested that the crp gene deletion could effectively attenuate the virulence of G. parasuis, and crp gene may act as an important potential target for the formulation of a novel vaccine against G. parasuis.

Glaesserella parasuis可引起严重的全身性疾病（Glasser 病），其特征是纤维蛋白性多浆膜炎、多关节炎和脑膜炎。cAMP 受体蛋白 (CRP) 是经过充分研究的全局调节蛋白之一，可以调节许多病原菌的毒力。我们之前的研究表明，crp基因参与了副猪生长速度、生物膜形成、胁迫耐受性、血清抗性和铁利用的调节。然而，crp基因是否可以调节副猪的毒力以前没有被分析过。在本研究中，观察到G. parasuis中的crp基因血清型 5 (HPS5) 参与调节 iPAM 细胞的粘附和侵袭能力，以及各种毒力相关因子的 mRNA 表达。它还具有诱导促炎细胞因子（IL-1α、IL-1β、IL-6、IL-8和TNF-α）mRNA表达的能力，促进核因子-κB（NF-κB）的活化) 和丝裂原活化蛋白激酶 (MAPK) 信号通路在猪肾上皮 (PK-15) 和永生化猪肺泡巨噬细胞 (iPAM) 细胞中，并有助于小鼠的致病性和器官定植。与野生型相比, 毒力相关因子在crp 中的表达突变株及其诱导促炎细胞因子 mRNA 表达的能力，以及 PK-15 和 iPAM 细胞中磷酸-p65 和磷酸-p38 的表达显着降低。此外，还发现与野生型相比，crp突变体的毒力显着降低。然而，与野生型相比，注意到Δcrp菌株对iPAM细胞的粘附和侵袭能力显着增强。这些结果表明，crp基因缺失可有效减弱副猪G.毒力，crp基因可作为研制副猪G.新型疫苗的重要潜在靶点。