关键词: 多杀性巴氏杆菌, 荚膜, 糖胺聚糖, 生物合成, 表达调控

Abstract:

Pasteurella multocida can be widely infected with a variety of animals, causing hemorrhagic septicemia or infectious pneumonia. P. multocida possess a viscous capsular polysaccharide on the cell surface, which is a critical structural component and virulence factor, and plays an important role in the interaction between bacteria and the host, promoting the adhesion of bacteria to the host surface and enhancing the virulence of the bacteria. The molecular structure of the P. multocida capsule is similar to that of vertebrate glycosaminoglycan, which is polymerized by repeated disaccharide units to form a linear polysaccharide chain, which is an important immunological material basis for molecular mimicry, resistance to phagocytosis, and immune evasion during the infection of the host. In recent years, a series of important research advances have been made in the biosynthesis and regulation mechanism aspects of P. multocida capsule, providing a certain basic knowledge for the molecular pathogenesis of P. multocida capsule, and supplying a theoretical basis for the development of the capsular polysaccharide vaccine of P. multocida. This paper systematically illuminates the biosynthesis and expression regulation mechanisms of P. multocida capsule, including the serotyping of the capsule, the composition and structure of the capsular polysaccharide, the biosynthesis gene cluster and function of the capsule, the molecular synthesis mechanism of capsular polysaccharide, the expression regulation mechanism of capsular biosynthesis gene cluster, a total of five aspects. According to the capsular antigen, P. multocida is divided into five capsular serogroups of A, B, D, E, and F. The type A capsule GAG component is hyaluronic acid; the type D is heparosan; the type F is chondroitin, which is repeatedly composed of its corresponding disaccharide unit [β-GlcUA/β-GlcNAc], [β-GlcUA/α-GlcNAc], [β-GlcUA/β-GalNAc], respectively; the type B capsular polysaccharide is composed of arabinose, mannose and galactose in a certain structural form, and the composition and chemical structure of type E capsular polysaccharide are uncertain. Genes related to the biosynthesis of A, B, D, E and F capsules of P. multocida exist in the form of gene clusters and are divided into three distinct functional regions, R1, R2 and R3; the R1 region is responsible for transporting the capsular polysaccharide, the R2 region is responsible for the activation of the monosaccharide and the assembly of the capsular polysaccharide, and the R3 region is responsible for the modification of capsular polysaccharide (phospholipid replacement); according to the structure and the number of genes of the R2 region, the biosynthetic gene clusters of the five capsules can be divided into two categories: type A, D and F are Class I, and R2 contains 4 genes; types B and E are Class II, and R2 contains 9 genes, and using the specific gene in the R2 region to design primers, the capsular serotype of P. multocida can be rapidly identified by PCR. The capsular GAG of P. multocida is synthesized in the cytoplasm, and then exported to the cell surface via the ABC transporter formed by the protein encoded by the R1 region, and tightly bound to the cell surface by covalent attachment to the phospholipid; during the biosynthesis of the P. multocida capsular GAG, the glycosyltransferase gene located in the R2 region determines the type of activated monosaccharide and the type of capsular polysaccharide after assembly. In the biosynthetic gene cluster of the P. multocida capsule, the R1 and R2 regions form an operon with the same transcriptional direction, while the R3 transcription direction is opposite, and the promoter regions of both are located on the DNA sequence between the R2 and R3 regions; the transcriptional process of the P. multocida capsular biosynthesis gene cluster is positive regulated by the Fis protein, and the translation process is mainly positive regulated by Hfq protein.

Key words: Pasteurella multocida, capsule, glycosaminoglycan, biosynthesis, expression regulation