Liandong Qu ^* Tenglin Xu Mingxing Kou Peili Cao Benjin Liu Yating Zheng Qian Jiang Jiasen Liu Hong-Tao Kang Mingfa Yang Dongchun Guo ^*

• Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China

Pasteurella multocida is a pathogenic bacterium known to cause hemorrhagic septicemia and pneumonia in poultry. Understanding virulent factors and analyzing the role of pro-inflammatory cytokines can help us elucidate the underlying pathogenesis. The PMCNA_RS00975 protein is a putative encapsuling protein encoded by a gene from a specific prophage island of the pathogenic strain C48-1 of P. multocida; however, its role in pathogenesis remains elusive. Pro-inflammatory cytokines have been implicated during P. multocida infection. In this study, the recombinant protein PMCNA_RS00975 P. multocida was soluble expressed and purified. Further subcellular localization indicated that the PMCNA_RS00975 protein was located at the outer membrane of P. multocida. Additionally, our experiments revealed that recombinant PMCNA_RS00975 protein promotes the secretion of the IL-6 pro-inflammatory cytokines triggered by TLR2 receptor via NF-κB and ERK1/2 signaling pathways in the macrophages. Therefore, PMCNA_RS00975 was identified as a virulence gene by constructing of this isogenic gene mutant, which pathogenicity decreased significantly in the mice model with P. multocida infection. Thus, the PMCNA_RS00975 was substantiated as a novel virulence factor in C48-1 strain of P. multocida, playing an important role in release of pro-inflammatory cytokines and pathogenicity of this pathogenic strain.