Enhanced Virulence of by : Evidence in Clinical Bloodstream Infections and Infected Zebrafish Embryos.

Coinfection with and results in higher mortality in animal studies. However, the pathogenesis and interplay between and in bloodstream infections (BSIs) is unclear. This study determines the clinical features and outcomes of mixed / (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 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 accounted for the main biofilm architecture, and increased its amount. Antibiotic tolerance in , which adhered to hyphae observed by scanning electron microscope, was demonstrated by the presence of wild-type co-biofilm. Upregulation in exotoxin genes of was evidenced by quantitative RT-PCR when a co-biofilm was formed with . 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 and during co-biofilm formation contributes to the high mortality rate.