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.
Highlights
Staphylococcus aureus is a human pathogenic bacterium that causes various human diseases, including suppurative diseases, pneumonia, and meningitis
When S. aureus cells were disrupted with lysostaphin and treated with 2% CHAPS, the recovered amount of phenol-soluble modulins (PSMs) was lower than that recovered by 2% CHAPS only or 6 M guanidine HCl (Fig 1A)
These results suggest that the PSM recovered by 2% CHAPS, 8 M urea, 6 M guanidine HCl, or 3 M LiCl derived from the S. aureus cell surface
Summary
Staphylococcus aureus is a human pathogenic bacterium that causes various human diseases, including suppurative diseases, pneumonia, and meningitis. Since the 1960s, methicillin-resistant S. aureus (MRSA) infection of immunocompromised patients in hospitals, i.e., hospitalassociated MRSA (HA-MRSA), has become a serious clinical problem. MRSA (CA-MRSA), a new type of MRSA that infects healthy persons in the community, was identified as a serious health issue in the mid 1990s [1]. PSMs comprise PSMα1, PSMα2, PSMα3, PSMα4, PSMβ1, PSMβ2, and δ-toxin (PSMγ), which are small polypeptides with an amphipathic alpha helical structure [3]. Among these PSMs, PSMα1, PSMα2, PSMα3, and δ-toxin have high lytic activity against neutrophils and erythrocytes [2]. Knockout of PSMα1–4 (PSMα1, PSMα2, PSMα3, and PSMα4) or δ-toxin decreases S. aureus virulence in a mouse infection model [2]. Clarifying PSM functions is important toward understanding the S. aureus infectious process at the molecular level
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