Dataset Information

Staphylococcus aureus Synergized with Candida albicans to Increase the Pathogenesis and Drug Resistance in Cutaneous Abscess and Peritonitis Murine Models.

ABSTRACT: The mixed species of Staphylococcus aureus and Candida albicans can cause infections on skin, mucosa or bloodstream; however, mechanisms of their cross-kingdom interactions related to pathogenesis and drug resistance are still not clear. Here an increase of S. aureus proliferation and biofilm formation was observed in S. aureus and C. albicans dual-species culture, and the synergistic pathogenic effect was then confirmed in both local (cutaneous abscess) and systemic infection (peritonitis) murine models. According to the transcriptome analysis of the dual-species culture, virulence factors of S. aureus were significantly upregulated. Surprisingly, the beta-lactams and vancomycin-resistant genes in S. aureus as well as azole-resistant genes in C. albicans were also significantly increased. The synergistic effects on drug resistance to both antibacterial and antifungal agents were further proved both in vitro and in cutaneous abscess and peritonitis murine models treated by methicillin, vancomycin and fluconazole. The synergistic interactions between S. aureus and C. albicans on pathogenesis and drug resistance highlight the importance of targeting the microbial interactions in polyspecies-associated infections.

SUBMITTER: Hu Y

PROVIDER: S-EPMC8398722 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Staphylococcus aureus Synergized with Candida albicans to Increase the Pathogenesis and Drug Resistance in Cutaneous Abscess and Peritonitis Murine Models.

Hu Yao Y Niu Yulong Y Ye Xingchen X Zhu Chengguang C Tong Ting T Zhou Yujie Y Zhou Xuedong X Cheng Lei L Ren Biao B

Pathogens (Basel, Switzerland) 20210816 8

The mixed species of Staphylococcus aureus and Candida albicans can cause infections on skin, mucosa or bloodstream; however, mechanisms of their cross-kingdom interactions related to pathogenesis and drug resistance are still not clear. Here an increase of S. aureus proliferation and biofilm formation was observed in S. aureus and C. albicans dual-species culture, and the synergistic pathogenic effect was then confirmed in both local (cutaneous abscess) and sy ...[more]

PMID: 34451500

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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 β-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.

Project description:Polymicrobial biofilms consisting of fungi and bacteria are frequently formed on endotracheal tubes and may contribute to development of ventilator associated pneumonia (VAP) in critically ill patients. This study aimed to determine the role of early Candida albicans biofilms in supporting dual-species (dual-kingdom) biofilm formation with respiratory pathogens in vitro, and investigated the effect of targeted antifungal treatment on bacterial cells within the biofilms. Dual-species biofilm formation between C. albicans and three respiratory pathogens commonly associated with VAP (Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus) was studied using quantitative PCR. It was shown that early C. albicans biofilms enhanced the numbers of E. coli and S. aureus (including methicillin resistant S. aureus; MRSA) but not P. aeruginosa within dual-species biofilms. Transwell assays demonstrated that contact with C. albicans was required for the increased bacterial cell numbers observed. Total Internal Reflection Fluorescence microscopy showed that both wild type and hyphal-deficient C. albicans provided a scaffold for initial bacterial adhesion in dual species biofilms. qPCR results suggested that further maturation of the dual-species biofilm significantly increased bacterial cell numbers, except in the case of E.coli with hyphal-deficient C. albicans (Ca_gcn5Δ/Δ). A targeted preventative approach with liposomal amphotericin (AmBisome®) resulted in significantly decreased numbers of S. aureus in dual-species biofilms, as determined by propidium monoazide-modified qPCR. Similar results were observed when dual-species biofilms consisting of clinical isolates of C. albicans and MRSA were treated with liposomal amphotericin. However, reductions in E. coli numbers were not observed following liposomal amphotericin treatment. We conclude that early C. albicans biofilms have a key supporting role in dual-species biofilms by enhancing bacterial cell numbers during biofilm maturation. In the setting of increasing antibiotic resistance, an important and unexpected consequence of antifungal treatment of dual-species biofilms, is the additional benefit of decreased growth of multi-drug resistant bacteria such as MRSA, which could represent a novel future preventive strategy.

Dataset Information

Staphylococcus aureus Synergized with Candida albicans to Increase the Pathogenesis and Drug Resistance in Cutaneous Abscess and Peritonitis Murine Models.

Publications

<i>Staphylococcus aureus</i> Synergized with <i>Candida albicans</i> to Increase the Pathogenesis and Drug Resistance in Cutaneous Abscess and Peritonitis Murine Models.

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