title: The two-component system Ihk/Irr contributes to the virulence of Streptococcus suis serotype 2 strain 05ZYH33 through alteration of the bacterial cell metabolism.
abstract: Streptococcus suis serotype 2 (S. suis 2) is an important zoonotic pathogen. It causes heavy economic losses in the pig-farming industry and can be associated with severe infections in humans, e.g. streptococcal toxic shock syndrome. Understanding its pathogenesis is critical for prevention and control of diseases caused by S. suis 2. In this study, we show that deletion of a two-component system (TCS), 05SSU1660/1661 (orthologues of the Ihk/Irr TCS of Streptococcus pyogenes), in S. suis 2 strain 05ZYH33 results in notable attenuation of virulence, as exemplified by reduced adherence to mucosal epithelium cells, increased elimination by macrophages, reduced ability to survive in an acidic or oxidative-stressed environment, and lowered pathogenicity in mice. Further analysis of differential proteomics profiles by two-dimensional electrophoresis revealed that while many previously well-known virulence factors, such as suilysin, autolysin and muraminidase-released protein, were not expressed differentially, cell metabolism was downregulated in the Ihk/Irr deletion mutant. In addition, the oxidative-stress response gene for manganese-dependent superoxide dismutase (MnSOD) was also repressed significantly in the mutant. Collectively, our data suggest that the Ihk/Irr TCS contributes to the virulence of S. suis 2 strain 05ZYH33, mainly through alteration of the bacterial cell metabolism.
authors.affiliation: Graduate University, Chinese Academy of Sciences, Beijing 100049, PR China.|CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, PR China.
authors.forename: Huiming
authors.initials: H
authors.lastname: Han
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, PR China.
authors.forename: Cuihua
authors.initials: C
authors.lastname: Liu
authors.affiliation: Beijing Proteomics Institute, Beijing 101318, PR China.|Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100029, PR China.
authors.forename: Quanhui
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Graduate University, Chinese Academy of Sciences, Beijing 100049, PR China.|CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, PR China.
authors.forename: Chunling
authors.initials: C
authors.lastname: Xuan
authors.affiliation: Graduate University, Chinese Academy of Sciences, Beijing 100049, PR China.|CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, PR China.
authors.forename: Beiwen
authors.initials: B
authors.lastname: Zheng
authors.affiliation: Department of Epidemiology, Research Institute for Medicine of Nanjing Command, Nanjing 210002, PR China.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Tang
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, PR China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Yan
authors.affiliation: School of Medicine, Tsinghua University, Beijing 100084, PR China.
authors.forename: Jingren
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Microbiology, Third Military Medical University, Chongqing 630030, PR China.|CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Graduate University, Chinese Academy of Sciences, Beijing 100049, PR China.|CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Cheng
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, PR China.
authors.forename: Guangwen
authors.initials: G
authors.lastname: Lu
authors.affiliation: Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, PR China.|Graduate University, Chinese Academy of Sciences, Beijing 100049, PR China.|CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, PR China.
authors.forename: George F
authors.initials: GF
authors.lastname: Gao
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D017353:Gene Deletion; D020869:Gene Expression Profiling; D051379:Mice; D018384:Oxidative Stress; D020543:Proteome / Q000032:analysis; D015398:Signal Transduction; D013290:Streptococcal Infections / Q000382:microbiology / Q000473:pathology; D017011:Streptococcus suis / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D013312:Stress, Physiological; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D020543:Proteome; D014157:Transcription Factors; D037521:Virulence Factors; C114259:iron response regulator protein, Bacteria