David H. Koch Institute for Integrative Cancer Research Massachusetts Institute of Technology 500 Main Street, Cambridge, MA, 02139, USA.
Department of Biotechnology Engineering, Ort Braude College, P.O. Box 78, Karmiel, 21982, Israel.
Adv Mater. 2018 Dec;30(51):e1803925. doi: 10.1002/adma.201803925. Epub 2018 Oct 17.
The emergence of antimicrobial resistance poses a major challenge to healthcare. Probiotics offer a potential alternative treatment method but are often incompatible with antibiotics themselves, diminishing their overall therapeutic utility. This work uses biofilm-inspired encapsulation of probiotics to confer temporary antibiotic protection and to enable the coadministration of probiotics and antibiotics. Probiotics are encapsulated within alginate, a crucial component of pseudomonas biofilms, based on a simple two-step alginate cross-linking procedure. Following exposure to the antibiotic tobramycin, the growth and metabolic activity of encapsulated probiotics are unaffected by tobramycin, and they show a four-log survival advantage over free probiotics. This results from tobramycin sequestration on the periphery of alginate beads which prevents its diffusion into the core but yet allows probiotic byproducts to diffuse outward. It is demonstrated that this approach using tobramycin combined with encapsulated probiotic has the ability to completely eradicate methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa in coculture, the two most widely implicated bacteria in chronic wounds.
抗菌药物耐药性的出现对医疗保健构成了重大挑战。益生菌提供了一种潜在的替代治疗方法,但通常与抗生素本身不兼容,降低了它们的整体治疗效果。本研究利用生物膜启发的益生菌包封技术,赋予益生菌暂时的抗生素保护,并实现益生菌和抗生素的联合应用。基于简单的两步海藻酸钠交联程序,将益生菌包封在海藻酸钠内,海藻酸钠是铜绿假单胞菌生物膜的关键组成部分。在暴露于抗生素妥布霉素后,包封的益生菌的生长和代谢活性不受妥布霉素的影响,与游离益生菌相比,其存活率高出四个对数级。这是由于妥布霉素被束缚在海藻酸钠珠的外围,阻止其扩散到核心,但允许益生菌副产物向外扩散。结果表明,妥布霉素联合包封益生菌的方法能够完全消除共培养物中的耐甲氧西林金黄色葡萄球菌和铜绿假单胞菌,这两种细菌是慢性伤口中最广泛涉及的细菌。