title: HP0197 contributes to CPS synthesis and the virulence of Streptococcus suis via CcpA.
abstract: Streptococcus suis serotype 2 (SS2), a major swine pathogen and an emerging zoonotic agent, has greatly challenged global public health. The encoding proteins with unknown functions the bacterium encodes are an obstruction to studies of the pathogenesis. A novel surface protective antigen HP0197 is one of these proteins which have no sequence homology to any known protein. In the present study, the protein was determined to be involved in bacterial virulence through an evaluation of the isogenic mutant (Δhp0197) in both mice and pigs. The experimental infection also indicated that Δhp0197 could be cleared easily during infection, which could be attributed to the reduced thickness of the capsular polysaccharides (CPS) and the significantly reduced phagocytotic resistance. Microarrays-based comparative transcriptome analysis suggested that the suppressed expression of the operon responsible for CPS synthesis might be reversed by CcpA activity, which controlled global regulation of carbon catabolite through the binding of the CcpA and HPr-Ser-46-P to the catabolite-responsive elements (cre) of the target operons. The hypothesis was approved by the fact that the purified FLAG-tagged HPr from WT stain exhibited a higher binding activity to cre with CcpA compared to the Δhp0197 by the Electrophoretic Mobility Shift Assay, suggesting lower level of phosphorylation of the phosphocarrier protein HPr at residue Ser-46 (HPr-Ser-46P) in Δhp0197. These indicated that HP0197 could enhance CcpA activity to control the expression of genes involved in carbohydrate utilization and CPS synthesis, thus contributing to the virulence of S. suis.
authors.affiliation: Unit of Animal Infectious Diseases, National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, People's Republic of China.
authors.forename: Anding
authors.initials: A
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.forename: Zhengzhi
authors.initials: Z
authors.lastname: Yuan
authors.forename: Ran
authors.initials: R
authors.lastname: Li
authors.forename: Cheng
authors.initials: C
authors.lastname: Liu
authors.forename: Hongbo
authors.initials: H
authors.lastname: Zhou
authors.forename: Huanchun
authors.initials: H
authors.lastname: Chen
authors.forename: Meilin
authors.initials: M
authors.lastname: Jin
mesh_terms: D000818:Animals; D016667:Bacterial Capsules / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D016923:Cell Death; D020869:Gene Expression Profiling; D051379:Mice; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010587:Phagocytosis; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System / Q000378:metabolism; D010768:Phosphoserine / Q000378:metabolism; D015203:Reproducibility of Results; D013290:Streptococcal Infections / Q000382:microbiology / Q000473:pathology; D017011:Streptococcus suis / Q000378:metabolism* / Q000472:pathogenicity*; D013552:Swine / Q000382:microbiology; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D010768:Phosphoserine; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System; C030182:phosphocarrier protein HPr