Background: There is a clear and urgent need for new tools to combat antibiotic resistance. Nano-phytoglycogen, a non-toxic, edible and biodegradable biomaterial, is a platform technology with many desirable properties that address the key limitations of conventional nanomaterials. Methods and Results: In this work, we conjugated antimicrobials to nano-phytoglycogen with the intent of enhancing delivery and reducing unwanted traits such as insolubility, toxicity etc. Conjugating Amphotericin B resulted in a soluble and functional antifungal-phytoglycogen bioconjugate with activity against Candida utilis. Nano-phytoglycogen was also modified to generate a number of derivatives showing strong antimicrobial activity against bacteria and yeast. One such derivative disrupted phenotypes associated with virulence of the major opportunistic pathogen Pseudomonas aeruginosa, and also inhibited its ability to attach to surfaces and form biofilms. Biofilms have been implicated in >70 % of all infections. Critically, growth as a biofilm results in enhanced tolerance to antibiotics and biocides, rendering the organisms less tractable to treatment. In addition, P. aeruginosa, which displays innate and adaptive resistance to diverse antibiotics, was rendered more susceptible to multiple classes of antibiotics - as were other bacteria and yeast. Combining modified nano-phytoglycogen with conventional antibiotics substantively enhanced performance as compared with using antibiotics alone, and abolished enhanced biofilm formation, an undesirable effect of sub-MIC antibiotic concentrations. Treatment of pre-formed biofilms with combinations of antibiotics and modified nano-phytoglycogen was also shown to be more effective than antibiotic alone. Conclusions: The data collectively indicates that phytoglycogen is a promising nanomaterial for developing novel therapies or co-therapeutics for the treatment and management of infectious disease.
Full conference title:
- ASM Microbe 2nd (2017)