抗生素治疗和吞噬细胞浸润对生物膜形成的影响：新型 PF 水凝胶模型的应用启示。
Effects of antibiotic treatment and phagocyte infiltration on development of biofilm-Insights from the application of a novel PF hydrogel model and .
机构信息
Costerton Biofilm Center, and Institute of International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Department of Clinical Microbiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
出版信息
Front Cell Infect Microbiol. 2022 Jul 26;12:826450. doi: 10.3389/fcimb.2022.826450. eCollection 2022.
BACKGROUND AND PURPOSE
Bacterial biofilm infections are major health issues as the infections are highly tolerant to antibiotics and host immune defenses. Appropriate biofilm models are important to develop and improve to make progress in future biofilm research. Here, we investigated the ability of PF hydrogel material to facilitate the development and study of biofilms and .
METHODS
Wild-type PAO1 bacteria were embedded in PF hydrogel situated or , and the following aspects were investigated: 1) biofilm development; 2) host immune response and its effect on the bacteria; and 3) efficacy of antibiotic treatment.
RESULTS
Microscopy demonstrated that developed typical biofilms inside the PF hydrogels and in mouse peritoneal cavities where the PF hydrogels were infiltrated excessively by polymorphonuclear leukocytes (PMNs). The bacteria remained at a level of ~10 colony-forming unit (CFU)/hydrogel for 7 days, indicating that the PMNs could not eradicate the biofilm bacteria. β-Lactam or aminoglycoside mono treatment at 64× minimal inhibitory concentration (MIC) killed all bacteria in day 0 biofilms, but not in day 1 and older biofilms, even at a concentration of 256× MIC. Combination treatment with the antibiotics at 256× MIC completely killed the bacteria in day 1 biofilms, and combination treatment in most of the cases showed significantly better bactericidal effects than monotherapies. However, in the case of the established biofilms, the mono and combination antibiotic treatments did not efficiently kill the bacteria.
CONCLUSION
Our results indicate that the bacteria formed typical biofilms in PF hydrogel and and that the biofilm bacteria were tolerant against antibiotics and host immunity. The PF hydrogel biofilm model is simple and easy to fabricate and highly reproducible with various application possibilities. We conclude that the PF hydrogel biofilm model is a new platform that will facilitate progress in future biofilm investigations, as well as studies of the efficacy of new potential medicine against biofilm infections.
背景与目的
细菌生物膜感染是一个主要的健康问题，因为这些感染对抗生素和宿主免疫防御具有高度耐受性。适当的生物膜模型对于未来的生物膜研究的发展和改进非常重要。在这里，我们研究了 PF 水凝胶材料促进生物膜和 发展和研究的能力。
方法
将野生型 PAO1 细菌嵌入 PF 水凝胶中，分别置于 和 ，并对以下方面进行了研究：1）生物膜的发展；2）宿主免疫反应及其对细菌的影响；3）抗生素治疗的效果。
结果
显微镜观察表明， 在 PF 水凝胶和被过度浸润多形核白细胞（PMN）的小鼠腹腔中，形成了典型的生物膜。细菌在 PF 水凝胶中保持在约 10 个菌落形成单位（CFU）/水凝胶的水平达 7 天，表明 PMN 无法清除生物膜细菌。β-内酰胺或氨基糖苷类单药治疗在 64×最小抑菌浓度（MIC）时可在第 0 天杀死所有生物膜细菌，但在第 1 天和更老的生物膜中无效，即使在 256×MIC 的浓度下也无效。在 256×MIC 时，抗生素联合治疗可完全杀死第 1 天的生物膜细菌，在大多数情况下，联合治疗比单药治疗具有更好的杀菌效果。然而，在已建立的生物膜的情况下，单药和联合抗生素治疗并不能有效地杀死细菌。
结论
我们的结果表明，细菌在 PF 水凝胶 中形成了典型的生物膜，生物膜细菌对抗生素和宿主免疫具有耐受性。PF 水凝胶生物膜模型简单、易于制备，具有高度可重复性，具有多种应用可能性。我们得出结论，PF 水凝胶生物膜模型是一个新的平台，将促进未来生物膜研究以及针对生物膜感染的新型潜在药物疗效的研究进展。
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