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Enhanced Virulence of Candida albicans by Staphylococcus aureus: Evidence in Clinical Bloodstream Infections and
Yen-Mu Wu1,2, Po-Yen Huang1, Yi-Chuan Cheng3,4
1Department of Internal Medicine, Division of Infectious Diseases, Chang Gung Memorial Hospital at Linkou Medical Center, Taoyuan City 333, Taiwan.
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.
Insights
Coinfections with Candida albicans and Staphylococcus aureus bloodstream infections (BSIs) significantly increase mortality. Co-biofilm formation enhances virulence, leading to worse patient outcomes.
Area of Science:
- Mycology
- Bacteriology
- Infectious Diseases
Background:
- Coinfection with Candida and Staphylococcus species is associated with increased mortality in animal models.
- The specific pathogenesis and interactions between Candida albicans and Staphylococcus aureus in bloodstream infections (BSIs) remain poorly understood.
Purpose of the Study:
- To investigate the clinical features and outcomes of mixed Candida albicans/Staphylococcus aureus (CA/SA) BSIs.
- To determine the role of biofilm formation in the pathogenesis of CA/SA coinfections.
Main Methods:
- Comparative analysis of demographics and outcomes between mixed CA/SA BSIs and monomicrobial Candida albicans BSIs.
- In vitro and in vivo biofilm formation analysis using scanning electron microscopy.
- Quantitative reverse transcription PCR (qRT-PCR) to assess gene expression.
Main Results:
- Mixed CA/SA BSIs showed a significantly higher mortality rate and shorter survival time compared to monomicrobial Candida albicans BSIs.
- Candida albicans formed the primary biofilm architecture, with Staphylococcus aureus increasing biofilm mass.
- Staphylococcus aureus exhibited increased antibiotic tolerance and exotoxin gene upregulation within the co-biofilm, adhering to Candida hyphae.
Conclusions:
- Mixed CA/SA BSIs are associated with increased patient mortality.
- Co-biofilm formation between Candida albicans and Staphylococcus aureus enhances virulence, contributing to higher mortality rates in bloodstream infections.

