Morphogenesis Is Not Required for Candida albicans-Staphylococcus aureus Intra-Abdominal Infection-Mediated Dissemination and Lethal Sepsis

Abstract

ABSTRACTIntra-abdominal polymicrobial infections cause significant morbidity and mortality. An established experimental mouse model ofStaphylococcus aureus-Candida albicansintra-abdominal infection results in ∼60% mortality within 48 h postinoculation, concomitant with amplified local inflammatory responses, while monomicrobial infections are avirulent. The purpose of this study was to characterize early local and systemic innate responses during coinfection and determine the role ofC. albicansmorphogenesis in lethality, a trait involved in virulence and physical interaction withS. aureus. Local and systemic proinflammatory cytokines were significantly elevated during coinfection at early time points (4 to 12 h) compared to those in monoinfection. In contrast, microbial burdens in the organs and peritoneal lavage fluid were similar between mono- and coinfected animals through 24 h, as was peritoneal neutrophil infiltration. After optimizing the model for 100% mortality within 48 h, using 3.5 × 107C. albicans(5× increase), coinfection withC. albicansyeast-locked or hypha-locked mutants showed similar mortality, dissemination, and local and systemic inflammation to the isogenic control. However, coinfection with the yeast-lockedC. albicansmutant given intravenously (i.v.) andS. aureusgiven intraperitoneally (i.p.) failed to induce mortality. These results suggest a unique intra-abdominal interaction between the host andC. albicans-S. aureusthat results in strong inflammatory responses, dissemination, and lethal sepsis, independent ofC. albicansmorphogenesis.