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.
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