title: Pathogenic Streptococcus strains employ novel escape strategy to inhibit bacteriostatic effect mediated by mammalian peptidoglycan recognition protein.
abstract: Pathogenic streptococcal species are responsible for some of the most lethal and prevalent animal and human infections. Previous reports have identified a candidate pathogenicity island (PAI) in two highly virulent clinical isolates of Streptococcus suis type 2, a causative agent of high-mortality streptococcal toxic shock syndrome. This PAI contains a type-IVC secretion system C subgroup (type-IVC secretion system) that is involved in the secretion of unknown pathogenic effectors that are responsible for streptococcal toxic shock syndrome caused by highly virulent strains of S. suis. Both virulence protein B4 and virulence protein D4 were demonstrated to be key components of this type-IVC secretion system. In this study, we identify a new PAI family across 3 streptococcal species; Streptococcus genomic island contains type-IV secretion system, which contains a genomic island type-IVC secretion system and a novel PPIase molecule, SP1. SP1 is shown to interact with a component of innate immunity, peptidoglycan recognition protein (PGLYRP-1) and to perturb the PGLYRP-1-mediated bacteriostatic effect by interacting with protein PGLYRP-1. Our study elucidates a novel mechanism by which bacteria escape by components of the innate immune system by secretion of the SP1 protein in pathogenic Streptococci, which then interacts with PGLYRP-1 from the host. Our results provide potential targets for the development of new antimicrobial drugs against bacteria with resistance to innate host immunity.
authors.affiliation: Translational Medicine Center, PLA Hospital No.454, Nanjing, China.
authors.forename: Jing
authors.identifier: 0000-0002-0079-0773
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Medical Microbiology Parasitology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Youjun
authors.identifier: 0000-0001-8083-0175
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Epidemiology, Medicinal Research Institute, Nanjing Military Command, Nanjing, China.
authors.forename: Changjun
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Medical Microbiology Parasitology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.|Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors.forename: Swaminath
authors.initials: S
authors.lastname: Srinivas
authors.affiliation: Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Translational Medicine Center, PLA Hospital No.454, Nanjing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liao
authors.affiliation: The Warren Alpert Medical School of Brown University, Providence, RI, USA.
authors.forename: Elaine
authors.initials: E
authors.lastname: He
authors.affiliation: Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA.
authors.forename: Shibo
authors.initials: S
authors.lastname: Jiang
authors.affiliation: PLA Research Institute of Clinical Laboratory Medicine, Nanjing General Hospital, Nanjing Military Command, Nanjing, China.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Tang
mesh_terms: D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D044404:Genomic Islands / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D019696:Peptidylprolyl Isomerase / Q000235:genetics* / Q000378:metabolism; D013290:Streptococcal Infections / Q000276:immunology* / Q000382:microbiology; D017011:Streptococcus suis / Q000276:immunology / Q000472:pathogenicity*; D000069319:Type IV Secretion Systems / Q000235:genetics*
chemical_list: D016207:Cytokines; C491878:PGLYRP1 protein, human; D000069319:Type IV Secretion Systems; D019696:Peptidylprolyl Isomerase
keywords: GI-type-IVC secretion system; PAI; PGRP; Streptococcus