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Morphogenesis is not required for Candida albicans-Staphylococcus aureus intra-abdominal infection-mediated dissemination and lethal sepsis.

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.

SUBMITTER: Nash EE

PROVIDER: S-EPMC4136217 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Morphogenesis is not required for Candida albicans-Staphylococcus aureus intra-abdominal infection-mediated dissemination and lethal sepsis.

Nash Evelyn E EE Peters Brian M BM Palmer Glen E GE Fidel Paul L PL Noverr Mairi C MC

Infection and immunity 20140602 8

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 morph ...[more]

PMID: 24891104

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Project description:Biofilm-associated polymicrobial infections, particularly those involving fungi and bacteria, are responsible for significant morbidity and mortality and tend to be challenging to treat. Candida albicans and Staphylococcus aureus specifically are considered leading opportunistic fungal and bacterial pathogens, respectively, mainly due to their ability to form biofilms on catheters and indwelling medical devices. However, the impact of mixed-species biofilm growth on therapy remains largely understudied. In this study, we investigated the influence of C. albicans secreted cell wall polysaccharides on the response of S. aureus to antibacterial agents in biofilm. Results demonstrated significantly enhanced tolerance for S. aureus to drugs in the presence of C. albicans or its secreted cell wall polysaccharide material. Fluorescence confocal time-lapse microscopy revealed impairment of drug diffusion through the mixed biofilm matrix. Using C. albicans mutant strains with modulated cell wall polysaccharide expression, exogenous supplementation, and enzymatic degradation, the C. albicans-secreted ?-1,3-glucan cell wall component was identified as the key matrix constituent providing the bacteria with enhanced drug tolerance. Further, antibody labeling demonstrated rapid coating of the bacteria by the C. albicans matrix material. Importantly, via its effect on the fungal biofilm matrix, the antifungal caspofungin sensitized the bacteria to the drugs. Understanding such symbiotic interactions with clinical relevance between microbial species in biofilms will greatly aid in overcoming the limitations of current therapies and in defining potential new targets for treating polymicrobial infections.The fungus Candida albicans and the bacterium Staphylococcus aureus are important microbial pathogens responsible for the majority of infections in hospitalized patients and are often coisolated from a host. In this study, we demonstrated that when grown together, the fungus provides the bacterium with enhanced tolerance to antimicrobial drugs. This process was mediated by polysaccharides secreted by the fungal cell into the environment. The biofilm matrix formed by these polysaccharides prevented penetration by the drugs and provided the bacteria with protection. Importantly, we show that by inhibiting the production of the fungal polysaccharides, a specific antifungal agent indirectly sensitized the bacteria to antimicrobials. Understanding the therapeutic implications of the interactions between these two diverse microbial species will aid in overcoming the limitations of current therapies and in defining new targets for treating complex polymicrobial infections.

Dataset Information

Morphogenesis is not required for Candida albicans-Staphylococcus aureus intra-abdominal infection-mediated dissemination and lethal sepsis.

Publications

Morphogenesis is not required for Candida albicans-Staphylococcus aureus intra-abdominal infection-mediated dissemination and lethal sepsis.

Similar Datasets

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