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Moreover, they are frequently coisolated from central venous catheters and deep-seated infections, including intra-abdominal sepsis. In this work, we have shown that coinfection with<jats:named-content content-type=\"genus-species\">C. albicans<\/jats:named-content>and<jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>is highly lethal, leading to &gt;80% mortality by day 1 postinfection, whereas monoinfection with<jats:named-content content-type=\"genus-species\">C. albicans<\/jats:named-content>or<jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>does not cause mortality. This infectious synergism is dependent on the expression of staphylococcal alpha-toxin, and secretion of this potent virulence factor is actually augmented by<jats:named-content content-type=\"genus-species\">C. albicans<\/jats:named-content>via an<jats:italic>agr<\/jats:italic>-dependent mechanism. Moreover, prophylactic neutralization of alpha-toxin with a monoclonal antibody is sufficient to elicit protection during coinfection. Therefore, we have demonstrated that a pathogenic fungus can enhance virulence determinants of a bacterium<jats:italic>in vivo<\/jats:italic>with devastating consequences to the host. 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