Enhanced Virulence of <i>Candida albicans</i> by <i>Staphylococcus aureus</i>: Evidence in Clinical Bloodstream Infections and Infected Zebrafish Embryos

Abstract

Coinfection with Candida and Staphylococcus results in higher mortality in animal studies. However, the pathogenesis and interplay between C. albicans and S. aureus in bloodstream infections (BSIs) is unclear. This study determines the clinical features and outcomes of mixed C. albicans/S. aureus (CA/SA) BSIs and biofilm formation on pathogenesis during coinfection. Demographics and outcomes for mixed BSIs and monomicrobial candidemia were compared. Compared to 115 monomicrobial C. albicans BSIs, 22 patients with mixed CA/SA BSIs exhibited a significantly higher mortality rate and shorter survival time. In vitro and in vivo biofilm analysis showed that C. albicans accounted for the main biofilm architecture, and S. aureus increased its amount. Antibiotic tolerance in S. aureus, which adhered to Candida hyphae observed by scanning electron microscope, was demonstrated by the presence of wild-type C. albicans co-biofilm. Upregulation in exotoxin genes of S. aureus was evidenced by quantitative RT-PCR when a co-biofilm was formed with C. albicans. Mixed CA/SA BSIs result in a higher mortality rate in patients and in vivo surrogate models experiments. This study demonstrates that the virulence enhancement of C. albicans and S. aureus during co-biofilm formation contributes to the high mortality rate.

Keywords

• mixed BSI
• virulence
• co-biofilm
• <i>Candida albicans</i>
• <i>Staphylococcus aureus</i>
• hyphal morphogenesis