Nine Staphylococcus aureus strains isolated from patients with toxic shock syndrome (TSS), two strains from non-disease-associated sources, and four strains from disease (not TSS)-associated sources were characterized for the intraperitoneal dose necessary to kill 50% of exposed animals (LD50) and toxic shock toxin production and studied for synergistic effects on mouse mortality and morbidity when combined with a sublethal dose of Candida albicans and inoculated intraperitoneally. Representative toxic shock toxin-producing strains (free of other enterotoxins) exhibited the following unique set of characteristics when inoculated intraperitoneally into mice and compared with all other strains tested: (i) lowest virulence when inoculated alone into mice as determined by the LD50; (ii) greatest synergistic decrease in LD50 (up to 70,000-fold as compared to up to 200-fold for other strains) when combined with C. albicans and injected intraperitoneally; and (iii) induced a characteristic, dose-independent, temporal death pattern in dually injected animals. When sublethal dual doses were used, animals receiving disease (TSS and not TSS)-associated S. aureus in combination with C. albicans developed symptoms, but some differences in symptomatologies, depending on the strain, were observed. The symptoms included conjunctivitis; gastrointestinal, neurological, and circulatory abnormalities; rash followed by desquamation; and patchy baldness. Although overlap in symptoms between animal treatment groups was observed, certain symptoms (neurological sequeae and petechial hemorrhages) were observed only in animals inoculated with a specific S. aureus strain combined with C. albicans. Animals receiving sublethal dual doses, which included non-disease-associated S. aureus, did not develop symptoms. When Staphylococcus epidermidis was combined with C. albicans and inoculated into mice, no synergistic effects on morbidity or mortality were observed
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