单月桂酸甘油酯纳米脂质体与吸附性抗菌肽联合应用对金黄色葡萄球菌生物膜的体外抗菌协同作用在体内并不存在。
Antimicrobial synergy of monolaurin lipid nanocapsules with adsorbed antimicrobial peptides against Staphylococcus aureus biofilms in vitro is absent in vivo.
机构信息
University of Groningen, University Medical Center Groningen, Department of Biomedical Engineering, P.O Box 196, 9700 AD Groningen, the Netherlands.
University of Groningen, University Medical Center Groningen, Department of Biomedical Engineering, P.O Box 196, 9700 AD Groningen, the Netherlands; State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Functional Polymer Materials, Ministry of Education, Institute of Polymer Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, PR China.
出版信息
J Control Release. 2019 Jan 10;293:73-83. doi: 10.1016/j.jconrel.2018.11.018. Epub 2018 Nov 19.
Bacterial infections are mostly due to bacteria in their biofilm-mode of growth, while penetrability of antimicrobials into infectious biofilms and increasing antibiotic resistance hamper infection treatment. In-vitro, monolaurin lipid nanocapsules (ML-LNCs) carrying adsorbed antimicrobial peptides (AMPs) displayed synergistic efficacy against planktonic Staphylococcus aureus, but it has not been demonstrated, neither in-vitro nor in-vivo, that such ML-LNCs penetrate into infectious S. aureus biofilms and maintain synergy with AMPs. This study investigates the release mechanism of AMPs from ML-LNCs and possible antimicrobial synergy of ML-LNCs with the AMPs DPK-060 and LL-37 against S. aureus biofilms in-vitro and in a therapeutic, murine, infected wound-healing model. Zeta potentials demonstrated that AMP release from ML-LNCs was controlled by the AMP concentration in suspension. Both AMPs demonstrated no antimicrobial efficacy against four staphylococcal strains in a planktonic mode, while a checkerboard assay showed synergistic antimicrobial efficacy when ML-LNCs and DPK-060 were combined, but not for combinations of ML-LNCs and LL-37. Similar effects were seen for growth reduction of staphylococcal biofilms, with antimicrobial synergy persisting only for ML-LNCs at the highest level of DPK-060 or LL-37 adsorption. Healing of wounds infected with bioluminescent S. aureus Xen36, treated with ML-LNCs alone, was faster when treated with PBS, while AMPs alone did not yield faster wound-healing than PBS. Faster, synergistic wound-healing due to ML-LNCs with adsorbed DPK-060, was absent in-vivo. Summarizing, antimicrobial synergy of ML-LNCs with adsorbed antimicrobial peptides as seen in-vitro, is absent in in-vivo healing of infected wounds, likely because host AMPs adapted the synergistic role of the AMPs added. Thus, conclusions regarding synergistic antimicrobial efficacy, should not be drawn from planktonic data, while even in-vitro biofilm data bear little relevance for the in-vivo situation.
细菌感染主要是由于其生物膜生长模式中的细菌引起的，而抗菌药物渗透到感染性生物膜中和抗生素耐药性的增加阻碍了感染的治疗。在体外，负载吸附抗菌肽（AMPs）的单月桂酸脂质纳米胶囊（ML-LNCs）对浮游金黄色葡萄球菌显示出协同功效，但尚未证明，无论是在体外还是体内，这种 ML-LNCs 能够渗透到感染的金黄色葡萄球菌生物膜中，并与 AMPs 保持协同作用。本研究旨在研究 AMPs 从 ML-LNCs 中的释放机制以及 ML-LNCs 与 AMPs DPK-060 和 LL-37 对金黄色葡萄球菌生物膜的体外和治疗性、感染性、伤口愈合模型中的可能抗菌协同作用。Zeta 电位表明，AMP 从 ML-LNCs 的释放受悬浮液中 AMP 浓度的控制。两种 AMPs 在浮游模式下对 4 株葡萄球菌均无抗菌功效，而棋盘试验显示 ML-LNCs 和 DPK-060 联合使用时具有协同抗菌功效，但 ML-LNCs 和 LL-37 联合使用时则没有。同样的效果也见于减少金黄色葡萄球菌生物膜的生长，只有在最高水平的 DPK-060 或 LL-37 吸附时，ML-LNCs 才能保持抗菌协同作用。单独用 ML-LNCs 处理感染生物发光金黄色葡萄球菌 Xen36 的伤口，用 PBS 处理时伤口愈合更快，而单独使用 AMPs 比用 PBS 处理时伤口愈合更快。由于 ML-LNCs 吸附的 DPK-060 而产生的协同性伤口愈合在体内不存在。综上所述，在体内感染性伤口愈合中，不存在 ML-LNCs 与吸附的抗菌肽的协同抗菌作用，这可能是因为宿主 AMPs 适应了添加的 AMPs 的协同作用。因此，不应从浮游数据中得出关于协同抗菌功效的结论，而即使是体外生物膜数据也与体内情况几乎没有相关性。
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