title: Roles of the Putative Type IV-like Secretion System Key Component VirD4 and PrsA in Pathogenesis ofStreptococcus suisType 2.
abstract: Streptococcus suistype 2 (SS2) is a zoonotic pathogen causing septic infection, meningitis and pneumonia in pigs and humans. SS2 may cause streptococcal toxic shock syndrome (STSS) probably due to excessive release of inflammatory cytokines. A previous study indicated that thevirD4gene in the putative type IV-like secretion system (T4SS) within the 89K pathogenicity island specific for recent epidemic strains contributed to the development of STSS. However, the functional basis of VirD4 in STSS remains unclear. Here we show that deletion ofvirD4led to reduced virulence as shown by about 65% higher LD50, lower bacterial load in liver and brain, and lower level of expression of inflammatory cytokines in mice and cell lines than its parent strain. The ΔVirD4 mutant was more easily phagocytosed, suggesting its role as an anti-phagocytic factor. Oxidative stress that mimic bacterial exposure to respiratory burst of phagocytes upregulated expression ofvirD4. Proteomic analysis identified 10 secreted proteins of significant differences between the parent and mutant strains under oxidative stress, including PrsA, a peptidyl-prolyl isomerase. The SS2 PrsA expressed inE. colicaused a dose-dependent cell death and increased expression of proinflammatory IL-1β, IL-6 and TNF-α in murine macrophage cells. Our data provide novel insights into the contribution of the VirD4 factor to STSS pathogenesis, possibly via its anti-phagocytic activity, upregulation of its expression upon oxidative stress and its involvement in increased secretion of PrsA as a cell death inducer and proinflammatory effector.
authors.affiliation: Zhejiang University Institute of Preventive Veterinary Medicine, and Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine Zhejiang, China.
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Zhejiang University Institute of Preventive Veterinary Medicine, and Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine Zhejiang, China.
authors.forename: Yunkai
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Zhejiang University Institute of Preventive Veterinary Medicine, and Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine Zhejiang, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Zhejiang University Institute of Preventive Veterinary Medicine, and Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine Zhejiang, China.
authors.forename: Lexin
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Zhejiang University Institute of Preventive Veterinary Medicine, and Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine Zhejiang, China.
authors.forename: Yuanxing
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Zhejiang University Institute of Preventive Veterinary Medicine, and Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine Zhejiang, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Zhejiang University Institute of Preventive Veterinary Medicine, and Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine Zhejiang, China.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Li
authors.affiliation: Zhejiang University Institute of Preventive Veterinary Medicine, and Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine Zhejiang, China.
authors.forename: Weihuan
authors.initials: W
authors.lastname: Fang
mesh_terms: D000818:Animals; D058491:Bacterial Load; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D021983:Cyclophilins / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000235:genetics; D044404:Genomic Islands; D006801:Humans; D007249:Inflammation / Q000276:immunology; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000235:genetics; D010446:Peptide Fragments / Q000378:metabolism; D010586:Phagocytes; D010587:Phagocytosis; D017384:Sequence Deletion; D012772:Shock, Septic / Q000276:immunology / Q000382:microbiology; D013290:Streptococcal Infections / Q000382:microbiology*; D017011:Streptococcus suis / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D000069319:Type IV Secretion Systems / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D010446:Peptide Fragments; D000069319:Type IV Secretion Systems; C052994:interleukin-1beta (163-171); D021983:Cyclophilins
keywords: PrsA; Streptococcus suis type 2; VirD4; anti- phagocytic; inflammatory response; streptococcal toxic shock syndrome