title: Functional analysis of c-di-AMP phosphodiesterase, GdpP, in Streptococcus suis serotype 2.
abstract: Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen that causes serious diseases in pigs and humans. GdpP protein is a recently discovered specific phosphodiesterase that degrades cyclic diadenosine monophosphate (c-di-AMP). It is widely distributed among the firmicutes phylum and altered expression of GdpP is associated with several phenotypes in various bacterial strains. We investigated the role of GdpP in physiology and virulence in SS2. An in-frame mutant of gdpP was constructed using homologous recombination and bacterial growth, biofilm formation, hemolytic activity, cell adherence and invasion, expression of virulence factors, and virulence were evaluated. Disruption of gdpP increased intracellular c-di-AMP level and affected growth and increased biofilm formation of SS2. Simultaneously, the gdpP mutant strain exhibited a significant decrease in hemolytic activity and adherence to and invasion of HEp-2 cells compared with the parental strain. Quantitative reverse transcriptase polymerase chain reaction indicated significantly reduced expression of the known virulence genes cps2, sly, fpbs, mrp, ef and gdh in the gdpP mutant. In murine infection models, the gdpP mutant strain was attenuated, and impaired bacterial growth was observed in specific organs. All these findings revealed a significant contribution of gdpP and its substrate (c-di-AMP) to the biology and virulence of SS2.
authors.affiliation: Department of Animal Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai Key Laboratory of Veterinary Biotechnology, Key Laboratory of Urban Agriculture (South) Ministry of Agriculture, Shanghai 200240, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Du
authors.affiliation: Department of Animal Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai Key Laboratory of Veterinary Biotechnology, Key Laboratory of Urban Agriculture (South) Ministry of Agriculture, Shanghai 200240, PR China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Ji
authors.affiliation: Department of Animal Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai Key Laboratory of Veterinary Biotechnology, Key Laboratory of Urban Agriculture (South) Ministry of Agriculture, Shanghai 200240, PR China.
authors.forename: Huiting
authors.initials: H
authors.lastname: An
authors.affiliation: Department of Animal Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai Key Laboratory of Veterinary Biotechnology, Key Laboratory of Urban Agriculture (South) Ministry of Agriculture, Shanghai 200240, PR China.
authors.forename: Yibo
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Animal Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai Key Laboratory of Veterinary Biotechnology, Key Laboratory of Urban Agriculture (South) Ministry of Agriculture, Shanghai 200240, PR China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of Animal Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai Key Laboratory of Veterinary Biotechnology, Key Laboratory of Urban Agriculture (South) Ministry of Agriculture, Shanghai 200240, PR China.
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Animal Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai Key Laboratory of Veterinary Biotechnology, Key Laboratory of Urban Agriculture (South) Ministry of Agriculture, Shanghai 200240, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Department of Animal Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai Key Laboratory of Veterinary Biotechnology, Key Laboratory of Urban Agriculture (South) Ministry of Agriculture, Shanghai 200240, PR China.
authors.forename: Hengan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Animal Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai Key Laboratory of Veterinary Biotechnology, Key Laboratory of Urban Agriculture (South) Ministry of Agriculture, Shanghai 200240, PR China. Electronic address: yanyaxian@sjtu.edu.cn.
authors.forename: Yaxian
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of Animal Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai Key Laboratory of Veterinary Biotechnology, Key Laboratory of Urban Agriculture (South) Ministry of Agriculture, Shanghai 200240, PR China. Electronic address: sunjhe@sjtu.edu.cn.
authors.forename: Jianhe
authors.initials: J
authors.lastname: Sun
mesh_terms: D000825:Animal Structures / Q000382:microbiology; D000818:Animals; D001422:Bacterial Adhesion; D018441:Biofilms / Q000254:growth & development; D015226:Dinucleoside Phosphates / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation; D017353:Gene Deletion; D020869:Gene Expression Profiling; D006094:Gram-Positive Bacteria; D006461:Hemolysis; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000382:microbiology; D006801:Humans; D051379:Mice; D010727:Phosphoric Diester Hydrolases / Q000235:genetics / Q000378:metabolism*; D065288:Serogroup; D013290:Streptococcal Infections / Q000382:microbiology / Q000473:pathology; D017011:Streptococcus suis / Q000145:classification / Q000201:enzymology* / Q000472:pathogenicity / Q000502:physiology*; D037521:Virulence Factors / Q000096:biosynthesis
chemical_list: D015226:Dinucleoside Phosphates; D037521:Virulence Factors; C528998:cyclic diadenosine phosphate; D010727:Phosphoric Diester Hydrolases
keywords: Cyclic diadenosine monophosphate; Pathogenicity; Streptococcus suis serotype 2; gdpP mutant