Enhanced Virulence of Candida albicans by Staphylococcus aureus: 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.

Candida albicansenhanceStaphylococcus aureusvirulence by progressive generation of new phenotypes

“…5A-B). This agrees with the lethal synergism observed from in vivo experiments of systemic and local infections after co-inoculation of both microorganisms (3, 9–11, 19, 20). Our results showed that G. mellonella larvae survival at 24 h decreased from 71.4% when infected with colony 8 to 0- 14% when infected with colonies 1 and 2, respectively.…”

“…In the case of C. albicans and S. aureus, it has long been known that their intraperitoneal coinfection has a synergistic effect on mouse mortality (9). Increased virulence of C. albicans and S. aureus co-infection has also been reported in zebrafish embryos, Galleria mellonella larvae, and patients with systemic infections (10,11). However, it was only recently that the major lethality driver and its mechanism of activation were identified.…”

Prevalence and resistance trends of Gram positive cocci Staphylococcus aereus and Enterococcus spp. in a tertiary care hospital

“…In addition, the majority of these patients (55.9%) were under treatment in the intensive care unit. It has been reported in previous studies that being in the intensive care unit will adversely affect both the risk of conversion to BSI of colonization, morbidity and mortality, since it indicates the presence of intravascular medical equipment applications, intensive drug therapy applications, and possibly underlying comorbidities that may be immunosuppressive 5,[17][18][19][20] .…”

Correlation of plasma procalcitonin and C-reactive protein levels with disease severity in critically ill patients with mixed-pathogen bloodstream infections of both Enterococcus spp. and Candida spp.

“…lead to higher morbidity and mortality than those caused by monomicrobial or polybacterial pathogens. 14 Pathogenic bacteria in the bloodstream release toxins and metabolites, thus provoking a systemic in ammatory response. 15 At present, procalcitonin (PCT) and C-reactive protein (CRP) are commonly used as in ammatory markers for the early diagnosis of BSIs.…”