Department of Chemical Sciences, Synthesis and Solid State Pharmaceutical Centre & Bernal Institute, University of Limerick, Limerick, Ireland.
Teagasc Food Research Centre, Moorepark, Fermoy, Co. Cork, Ireland; APC Microbiome Ireland, University College Cork, Cork, Ireland.
Int J Pharm. 2019 Mar 10;558:9-17. doi: 10.1016/j.ijpharm.2018.12.035. Epub 2018 Dec 19.
There is huge global concern surrounding the emergence of antimicrobial resistant bacteria and this is resulting in an inability to treat infectious diseases. This is due to a lack of new antimicrobials coming to the market and irresponsible use of traditional antibiotics. Bactofencin A, a novel antimicrobial peptide which shows potential as an antibiotic, is susceptible to enzyme degradation. To improve its solution stability and inherent activity, bactofencin A was loaded onto a traditional silica mesoporous matrix, SBA-15, and a periodic mesoporous organosilane, MSE. The loading of bactofencin A was considerably higher onto SBA-15 than MSE due to the hydrophilic nature of SBA-15. While there was no detectable peptide released from SBA-15 into phosphate buffered saline and only 20% of the peptide loaded onto MSE was released, the loaded matrices showed enhanced activity compared to the free peptide during in vitro antimicrobial assays. In addition, the mesoporous matrices were found to protect bactofencin A against enzymatic degradation where results showed that the SBA-15 and MSE with loaded bactofencin A exposed to trypsin inhibited the growth of S. aureus while a large decrease in activity was observed for free bactofencin upon exposure to trypsin. Thus, the activity and stability of bactofencin A can be enhanced using mesoporous matrices and these matrices may enable its potential development as a novel antibiotic. This work also shows that in silico studies looking at surface functional group and size complementarity between the peptide and the protective matrix could enable the systemic selection of a mesoporous matrix for individual bacteriocins with potential antimicrobial therapeutic properties.
全球范围内对抗菌药物耐药菌出现的问题感到担忧，这导致了传染病无法得到治疗。这是由于新的抗菌药物无法进入市场，以及传统抗生素的不合理使用。Bactofencin A 是一种新型抗菌肽，具有成为抗生素的潜力，但易被酶降解。为了提高其溶液稳定性和固有活性，将 bactofencin A 负载到传统的硅基介孔基质 SBA-15 和周期性介孔有机硅 MSE 上。由于 SBA-15 的亲水性，bactofencin A 被负载到 SBA-15 上的量要明显高于 MSE。虽然从 SBA-15 中没有检测到肽释放到磷酸盐缓冲液中，只有 20%负载到 MSE 的肽被释放，但在体外抗菌测定中，负载的基质显示出比游离肽更高的活性。此外，介孔基质被发现可以保护 bactofencin A 免受酶降解的影响，结果表明，暴露于胰蛋白酶的负载有 bactofencin A 的 SBA-15 和 MSE 抑制了金黄色葡萄球菌的生长，而暴露于胰蛋白酶的游离 bactofencin A 的活性则大大降低。因此，介孔基质可以增强 bactofencin A 的活性和稳定性，并且这些基质可以使其作为新型抗生素的潜在开发成为可能。这项工作还表明，通过对肽和保护基质之间的表面官能团和大小互补性进行计算机模拟研究，可以针对具有潜在抗菌治疗特性的个体细菌素，在系统上选择介孔基质。
