Bacterial biofilm infections, particularly those of
Pseudomonas aeruginosa
(PA), have high rates of antimicrobial tolerance and are commonly found in chronic wound and cystic fibrosis lung infections. Combination therapeutics that act synergistically can overcome antimicrobial tolerance; however, the delivery of multiple therapeutics at relevant dosages remains a challenge. We therefore developed a nanoscale drug carrier for antimicrobial codelivery by combining approaches from polyelectrolyte nanocomplex (NC) formation and layer-by-layer electrostatic self-assembly. This strategy led to NC drug carriers loaded with tobramycin antibiotics and antimicrobial silver nanoparticles (AgTob-NCs). AgTob-NCs displayed synergistic enhancements in antimicrobial activity against both planktonic and biofilm PA cultures, with positively charged NCs outperforming negatively charged formulations. NCs were evaluated in mouse models of lung infection, leading to reduced bacterial burden and improved survival outcomes. This approach therefore shows promise for nanoscale therapeutic codelivery to treat recalcitrant bacterial infections.
Thermolabile nature of commercially available vaccines necessitates their storage, transportation, and dissemination under refrigerated condition. Maintenance of continuous cold chain at every step increases the final cost of vaccines. Any breach in the cold chain even for a short duration results in the need to discard the vaccines. As a result, there is a pressing need for the development of thermostable vaccines. In this proof-of-concept study, we showed that
E. coli
curli-green fluorescent fusion protein remains stable in freeze-dried yeast powder for more than 18 and 12 months when stored at 30 °C and 37 °C respectively. Stability of the heterologous protein remains unaffected during the process of heat-inactivation and lyophilization. The mass of lyophilized yeast powder remains almost unchanged during the entire period of storage and expressed protein remains intact even after two cycles of freeze and thaws. The protease-deficient strain appears ideal for the development of whole recombinant yeast-based vaccines. The cellular abundance of expressed antigen in dry powder after a year was comparable to freshly lyophilized cells. Scanning electron microscopy showed the intact nature of cells in powdered form even after a year of storage at 30 °C. Observation made in this study showed that freeze-dry yeast powder can play a vital role in the development of thermostable vaccines.
Key Points
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Yeast-based vaccines can overcome problem of cold chain associated with conventional vaccines
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Lyophilized yeast powder can be a simple way for long-term storage of immunogen(s)
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Protease deficient strain is important for whole recombinant yeast-based vaccines
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