Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada.
Department of Microbiology and Immunology, University of Otago, Dunedin, Otago, New Zealand.
NPJ Biofilms Microbiomes. 2021 Jan 25;7(1):8. doi: 10.1038/s41522-020-00182-4.
Bacterial biofilms cause 65% of all human infections and are highly resistant to antibiotic therapy but lack specific treatments. To provide a human organoid model for studying host-microbe interplay and enabling screening for novel antibiofilm agents, a human epidermis organoid model with robust methicillin-resistant Staphylococcus aureus (MRSA) USA300 and Pseudomonas aeruginosa PAO1 biofilm was developed. Treatment of 1-day and 3-day MRSA and PAO1 biofilms with antibiofilm peptide DJK-5 significantly and substantially reduced the bacterial burden. This model enabled the screening of synthetic host defense peptides, revealing their superior antibiofilm activity against MRSA compared to the antibiotic mupirocin. The model was extended to evaluate thermally wounded skin infected with MRSA biofilms resulting in increased bacterial load, cytotoxicity, and pro-inflammatory cytokine levels that were all reduced upon treatment with DJK-5. Combination treatment of DJK-5 with an anti-inflammatory peptide, 1002, further reduced cytotoxicity and skin inflammation.
细菌生物膜导致 65%的人类感染，并且对抗生素治疗具有高度抗性，但缺乏特定的治疗方法。为了提供一种用于研究宿主-微生物相互作用的人类类器官模型，并能够筛选新型抗生物膜剂，开发了一种具有稳健耐甲氧西林金黄色葡萄球菌（MRSA）USA300 和铜绿假单胞菌 PAO1 生物膜的人类表皮类器官模型。用抗生物膜肽 DJK-5 处理 1 天和 3 天的 MRSA 和 PAO1 生物膜可显著且大量减少细菌负担。该模型可用于筛选合成宿主防御肽，揭示其对 MRSA 的抗生物膜活性优于抗生素莫匹罗星。该模型扩展到评估感染 MRSA 生物膜的热损伤皮肤，导致细菌负荷、细胞毒性和促炎细胞因子水平增加，而用 DJK-5 处理可降低这些水平。DJK-5 与抗炎肽 1002 的联合治疗进一步降低了细胞毒性和皮肤炎症。
