title: Cell-Surface Phenol Soluble Modulins Regulate Staphylococcus aureus Colony Spreading.
abstract: Staphylococcus aureus produces phenol-soluble modulins (PSMs), which are amphipathic small peptides with lytic activity against mammalian cells. We previously reported that PSMα1-4 stimulate S. aureus colony spreading, the phenomenon of S. aureus colony expansion on the surface of soft agar plates, whereas δ-toxin (Hld, PSMγ) inhibits colony-spreading activity. In this study, we revealed the underlying mechanism of the opposing effects of PSMα1-4 and δ-toxin in S. aureus colony spreading. PSMα1-4 and δ-toxin are abundant on the S. aureus cell surface, and account for 18% and 8.5% of the total amount of PSMα1-4 and δ-toxin, respectively, in S. aureus overnight cultures. Knockout of PSMα1-4 did not affect the amount of cell surface δ-toxin. In contrast, knockout of δ-toxin increased the amount of cell surface PSMα1-4, and decreased the amount of culture supernatant PSMα1-4. The δ-toxin inhibited PSMα3 and PSMα2 binding to the S. aureus cell surface in vitro. A double knockout strain of PSMα1-4 and δ-toxin exhibited decreased colony spreading compared with the parent strain. Expression of cell surface PSMα1-4, but not culture supernatant PSMα1-4, restored the colony-spreading activity of the PSMα1-4/δ-toxin double knockout strain. Expression of δ-toxin on the cell surface or in the culture supernatant did not restore the colony-spreading activity of the PSMα1-4/δ-toxin double knockout strain. These findings suggest that cell surface PSMα1-4 promote S. aureus colony spreading, whereas δ-toxin suppresses colony-spreading activity by inhibiting PSMα1-4 binding to the S. aureus cell surface.
authors.affiliation: Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Kizaki
authors.affiliation: Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Omae
authors.affiliation: Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Tabuchi
authors.affiliation: Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Sekimizu
authors.affiliation: Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Chikara
authors.identifier: http://orcid.org/0000-0002-2895-3386
authors.initials: C
authors.lastname: Kaito
mesh_terms: D001427:Bacterial Toxins / Q000096:biosynthesis* / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D055785:Gene Knockdown Techniques; D019800:Phenol; D013211:Staphylococcus aureus / Q000235:genetics / Q000254:growth & development*
chemical_list: D001427:Bacterial Toxins; C025971:staphylococcal delta toxin; D019800:Phenol