title: Streptolysin S contributes to group A streptococcal translocation across an epithelial barrier.
abstract: Group A Streptococcus pyogenes (GAS) is a human pathogen that causes local suppurative infections and severe invasive diseases. Systemic dissemination of GAS is initiated by bacterial penetration of the epithelial barrier of the pharynx or damaged skin. To gain insight into the mechanism by which GAS penetrates the epithelial barrier, we sought to identify both bacterial and host factors involved in the process. Screening of a transposon mutant library of a clinical GAS isolate recovered from an invasive episode allowed identification of streptolysin S (SLS) as a novel factor that facilitates the translocation of GAS. Of note, the wild type strain efficiently translocated across the epithelial monolayer, accompanied by a decrease in transepithelial electrical resistance and cleavage of transmembrane junctional proteins, including occludin and E-cadherin. Loss of integrity of intercellular junctions was inhibited after infection with a deletion mutant of the sagA gene encoding SLS, as compared with those infected with the wild type strain. Interestingly, following GAS infection, calpain was recruited to the plasma membrane along with E-cadherin. Moreover, bacterial translocation and destabilization of the junctions were partially inhibited by a pharmacological calpain inhibitor or genetic interference with calpain. Our data indicate a potential function of SLS that facilitates GAS invasion into deeper tissues via degradation of epithelial intercellular junctions in concert with the host cysteine protease calpain.
authors.affiliation: Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Sumitomo
authors.forename: Masanobu
authors.initials: M
authors.lastname: Nakata
authors.forename: Miharu
authors.initials: M
authors.lastname: Higashino
authors.forename: Yingji
authors.initials: Y
authors.lastname: Jin
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Terao
authors.forename: Yukako
authors.initials: Y
authors.lastname: Fujinaga
authors.forename: Shigetada
authors.initials: S
authors.lastname: Kawabata
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D018938:Caco-2 Cells; D015820:Cadherins / Q000378:metabolism; D002154:Calpain / Q000378:metabolism; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism* / Q000382:microbiology; D010614:Pharynx / Q000378:metabolism / Q000382:microbiology; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000382:microbiology; D013290:Streptococcal Infections / Q000201:enzymology* / Q000235:genetics; D013297:Streptococcus pyogenes / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity*; D013301:Streptolysins / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D015820:Cadherins; D013301:Streptolysins; C026050:streptolysin S; D002154:Calpain