PMCNA_RS00975 activates NF-κB and ERK1/2 through TLR2 and contributes to the virulence of Pasteurella multocida

• Published in: Frontiers in cellular and infection microbiology Vol. 14; p. 1469304
• Main Authors: Xu, Tenglin, Kou, Mingxing, Cao, Peili, Liu, Benjin, Zheng, Yating, Jiang, Qian, Liu, Jiasen, Kang, Hongtao, Yang, Mingfa, Guo, Dongchun, Qu, Liandong
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 15-10-2024
• Subjects: Animals; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Cellular and Infection Microbiology; Cytokines - metabolism; Disease Models, Animal; Female; Interleukin-6 - metabolism; Macrophages - microbiology; MAP Kinase Signaling System; Mice; NF-kappa B - metabolism; Pasteurella Infections - microbiology; Pasteurella multocida; Pasteurella multocida - genetics; Pasteurella multocida - metabolism; Pasteurella multocida - pathogenicity; PMCNA_RS00975; proinflammatory cytokines; Prophages - genetics; RAW 264.7 Cells; signaling pathway; Toll-Like Receptor 2 - genetics; Toll-Like Receptor 2 - metabolism; Virulence; virulence factor; Virulence Factors - genetics; Virulence Factors - metabolism; PMCNA_RS00975; signaling pathway; proinflammatory cytokines; virulence factor; Pasteurella multocida
• ISSN: 2235-2988; 2235-2988
• DOI: 10.3389/fcimb.2024.1469304

is a pathogenic bacterium known to cause hemorrhagic septicemia and pneumonia in poultry. Reports have indicated that certain proteins, either directly involved in or regulating iron metabolism, are important virulence factors of
. Therefore, understanding virulent factors and analyzing the role of pro-inflammatory cytokines can help us elucidate the underlying pathogenesis.
In this study, the PMCNA_RS00975 protein, a putative encapsuling protein encoded by a gene from a specific prophage island of the pathogenic strain
of
, was investigated. To further explore the impact of the PMCNA_RS00975 protein on pathogenicity, a
gene mutant of
strain
was constructed using positive selection technology. Subcellular localization was performed to determine the location of the PMCNA_RS00975 protein within
The recombinant protein PMCNA_RS00975 of
was soluble expressed, purified, and its role in pro-inflammatory cytokines was investigated.
The mutant exhibited significantly reduced pathogenicity in the mice model. Furthermore, subcellular localization indicated that the PMCNA_RS00975 protein was located at the outer membrane and expressed during infection of
Additionally, our experiments revealed that recombinant PMCNA_RS00975 protein promotes the secretion of the IL-6 pro-inflammatory cytokines triggered by the TLR2 receptor via NF-κB and ERK1/2 signaling pathways in the macrophages.
This study identified a novel virulence factor in the
strain, providing a basis for understanding the pathogenesis and directions for the development of attenuated vaccines against