Commensal Protection of Staphylococcus aureus against Antimicrobials by Candida albicans Biofilm Matrix.
Commensal Protection of Staphylococcus aureus against Antimicrobials by Candida albicans Biofilm Matrix.
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DOI：
10.1128/mbio.01365-16
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发表时间：
2016-10-11
期刊：
影响因子：
6.4
通讯作者：
Jabra-Rizk MA
中科院分区：
文献类型：
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作者：
Kong EF;Tsui C;Kucharíková S;Andes D;Van Dijck P;Jabra-Rizk MA
生物被膜相关的多种微生物感染，特别是涉及真菌和细菌的感染，是导致显著发病率和死亡率的原因，并且往往具有治疗挑战性。白色念珠菌和金黄色葡萄球菌被认为分别是主要的机会性真菌和细菌病原体，主要是由于它们能够在导管和留置医疗器械上形成生物被膜。然而，混合物种生物膜生长对治疗的影响在很大程度上仍未得到充分研究。在这项研究中，我们研究了白念珠菌分泌的细胞壁多糖对金黄色葡萄球菌对生物膜中抗菌剂的反应的影响。结果表明，在白色念珠菌或其分泌的细胞壁多糖物质存在下，金黄色葡萄球菌对药物的耐受性显著增强。荧光共聚焦延时显微镜显示，通过混合生物膜基质的药物扩散受损。使用具有调节的细胞壁多糖表达、外源补充和酶降解的白色念珠菌突变菌株，白色念珠菌分泌的β-1，3-葡聚糖细胞壁组分被鉴定为提供细菌增强的药物耐受性的关键基质组分。此外，抗体标记证明细菌被白色念珠菌基质材料快速包被。重要的是，通过其对真菌生物膜基质的作用，抗真菌剂卡泊芬净使细菌对药物敏感。了解这种共生相互作用与生物膜中微生物物种之间的临床相关性将大大有助于克服目前疗法的局限性，并确定治疗多微生物感染的潜在新靶点。真菌白色念珠菌和细菌金黄色葡萄球菌是导致住院患者中大多数感染的重要微生物病原体，并且通常从宿主中共分离。在这项研究中，我们证明了当一起生长时，真菌为细菌提供了增强的抗微生物药物耐受性。该过程由真菌细胞分泌到环境中的多糖介导。由这些多糖形成的生物膜基质阻止药物渗透并为细菌提供保护。重要的是，我们表明，通过抑制真菌多糖的产生，一种特定的抗真菌剂间接使细菌对抗菌剂敏感。了解这两种不同微生物之间相互作用的治疗意义将有助于克服当前疗法的局限性，并确定治疗复杂多微生物感染的新靶点。
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.