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Published on: November 6, 2020
Morphogenesis is not required for Candida albicans-Staphylococcus aureus intra-abdominal infection-mediated
Evelyn E Nash1, Brian M Peters2, Glen E Palmer1
1Department of Microbiology, Immunology, and Parasitology, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
Abstract:
Intra-abdominal polymicrobial infections cause significant morbidity and mortality. An established experimental mouse model of Staphylococcus aureus-Candida albicans intra-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 of C. albicans morphogenesis in lethality, a trait involved in virulence and physical interaction with S. 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 × 10(7) C. albicans (5× increase), coinfection with C. albicans yeast-locked or hypha-locked mutants showed similar mortality, dissemination, and local and systemic inflammation to the isogenic control. However, coinfection with the yeast-locked C. albicans mutant given intravenously (i.v.) and S. aureus given intraperitoneally (i.p.) failed to induce mortality. These results suggest a unique intra-abdominal interaction between the host and C. albicans-S. aureus that results in strong inflammatory responses, dissemination, and lethal sepsis, independent of C. albicans morphogenesis.
Insights
Polymicrobial infections with Staphylococcus aureus and Candida albicans cause lethal sepsis. This study found that C. albicans's shape (morphogenesis) does not influence the severe inflammatory response or mortality during intra-abdominal coinfection.
Area of Science:
- Infectious Diseases
- Immunology
- Microbiology
Background:
- Intra-abdominal polymicrobial infections involving Staphylococcus aureus and Candida albicans lead to high mortality.
- Monomicrobial infections with these pathogens are generally avirulent in established mouse models.
- Understanding the early innate immune response during coinfection is crucial for developing effective treatments.
Purpose of the Study:
- To characterize early local and systemic innate immune responses during Staphylococcus aureus-Candida albicans coinfection.
- To determine the role of Candida albicans morphogenesis (yeast-to-hypha transition) in the lethality of intra-abdominal coinfection.
- To investigate the interaction between host immunity and microbial factors in lethal sepsis.
Main Methods:
- Established a mouse model of Staphylococcus aureus-Candida albicans intra-abdominal coinfection, optimizing for 100% mortality within 48 hours.
- Administered wild-type and morphologically locked (yeast-locked or hypha-locked) Candida albicans mutants alongside Staphylococcus aureus.
- Measured local and systemic proinflammatory cytokine levels, microbial burdens, and neutrophil infiltration at early time points (4-12 hours).
Main Results:
- Coinfection significantly elevated local and systemic proinflammatory cytokines compared to monoinfection within 4-12 hours.
- Microbial burdens and neutrophil infiltration were similar between mono- and coinfected groups through 24 hours.
- Candida albicans morphogenesis (yeast-locked or hypha-locked) did not affect mortality, dissemination, or inflammation, except when yeast-locked mutants were administered intravenously.
Conclusions:
- The lethal outcome of Staphylococcus aureus-Candida albicans intra-abdominal coinfection is driven by a potent host inflammatory response independent of Candida albicans morphogenesis.
- A unique intra-abdominal interaction between the host, Staphylococcus aureus, and Candida albicans leads to disseminated, lethal sepsis.
- Further research into this specific host-pathogen interaction is warranted to identify therapeutic targets.
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