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.

Catabolite control protein A is an important regulator of metabolism in Streptococcus suis type 2

“…This is reminiscent of a functional study in Streptococcus pneumoniae, which showed that CcpA is a master regulator of catabolism and virulence (19). A notable impact on the capsule synthesis and virulence properties of S. suis has also been shown (20). The LC-MS-based metabolomics experiments in the present study suggested that CcpA is involved in the regulation of amino acid metabolism, which may affect the metabolic fitness and is in accordance with the findings of other studies (21).…”

TREM-1 Signaling Promotes Host Defense during the Early Stage of Infection with Highly Pathogenic Streptococcus suis

“…S. suis serotype 2 strain 05ZY (also known as SC-19) was isolated from the brain of a diseased piglet during the outbreak of S. suis diseases in China in 2005. The strain expresses muramidase-released protein, extracellular protein factor, and suilysin and is highly pathogenic to mice and pigs, causing STSLS (42,43). RAW264.7 mouse macrophage cells were purchased from ATCC (TIB-71) and maintained in Dulbecco's modified Eagle's medium supplemented with 10% fetal calf serum at 37°C and 5% CO 2 .…”

Regulating the Intersection of Metabolism and Pathogenesis in Gram-positive Bacteria

“…A S. pneumoniae ccpA mutant shows reduced expression of the capsular polysaccharide locus (105) and is highly attenuated for mouse nasopharyngeal and lung infection (106). Indirect evidence that S. suis CcpA controls capsule biosynthesis came from analysis of the effect of a mutation in a virulence-associated surface protein on HPr phosphorylation at serine-46 (107). In S. mutans , the major cause of dental caries, a ccpA mutant produces more acid than its parent, grows better at low pH, and excretes acid more rapidly, indicating that CcpA normally holds the cariogenic potential of S. mutans in check when rapidly metabolizable carbon sources are in excess (108).…”