title: Multidrug-Resistance Transporter AbcA Secretes Staphylococcus aureus Cytolytic Toxins.
abstract: Phenol-soluble modulins (PSMs) are Staphylococcus aureus cytolytic toxins that lyse erythrocytes and neutrophils and have important functions in the S. aureus infectious process. The molecular mechanisms of PSM secretion, however, are not well understood. Here we report that knockout of the multidrug-resistance ABC transporter AbcA, which contributes to S. aureus resistance against antibiotics and chemicals, diminished the secreted amount of PSM, leading to the accumulation of PSM in the intracellular fraction. The amount of PSM in the culture supernatants of the abcA knockout mutants was restored by introduction of the wild-type abcA gene, whereas it was not completely restored by introduction of mutant abcA genes encoding AbcA mutant proteins carrying amino acid substitutions in the adenosine triphosphate binding motifs. The abcA knockout mutant exhibited attenuated virulence in a mouse systemic infection model. These findings suggest that the multidrug resistance transporter AbcA secretes PSMs and contributes to S. aureus virulence.
authors.affiliation: Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Japan.
authors.forename: Hirono
authors.initials: H
authors.lastname: Yoshikai
authors.affiliation: Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of 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, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of 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, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Sekimizu
authors.affiliation: Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Japan.
authors.forename: Chikara
authors.initials: C
authors.lastname: Kaito
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D051379:Mice; D053038:Quorum Sensing / Q000502:physiology; D013203:Staphylococcal Infections / Q000382:microbiology* / Q000473:pathology; D013211:Staphylococcus aureus / Q000378:metabolism* / Q000472:pathogenicity; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014774:Virulence
chemical_list: D018528:ATP-Binding Cassette Transporters; C095698:Agr protein, Staphylococcus aureus; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D015534:Trans-Activators
keywords: Staphylococcus aureus; cytolytic toxins; multidrug resistance transporter; phenol-soluble modulins