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Jet nebulization of bacteriophages with different tail morphologies - Structural effects
Sharon Shui Yee Leung1, Nicholas B Carrigy2, Reinhard Vehring2
1Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia; School of Pharmacy, The Chinese University of Hong Kong, Shatin, Hong Kong.
International Journal of Pharmaceutics
|November 17, 2018
Summary
Jet nebulization damages bacteriophage (phage) structure, reducing infectivity. Tail length is crucial for selecting phages for inhaled therapies, as longer-tailed phages like Siphoviridae are more susceptible to structural damage.
Area of Science:
- Microbiology
- Biotechnology
- Drug Delivery
Background:
- Bacteriophage (phage) therapy is a promising alternative to antibiotics.
- Jet nebulization is a common method for delivering inhaled therapies.
- Previous studies indicated structural changes in myovirus PEV44 after jet nebulization, affecting infectivity.
Purpose of the Study:
- To investigate the impact of jet nebulization on the structure and infectivity of tailed phages from three different families: Podoviridae, Myoviridae, and Siphoviridae.
- To correlate observed structural changes with loss of phage infectivity.
- To assess the suitability of different phage families for inhaled therapy via jet nebulization.
Main Methods:
- Exposure of Podoviridae (PEV2), Myoviridae (PEV40), and Siphoviridae (D29) phages to jet nebulization.
- Analysis of phage structural integrity using Transmission Electron Microscopy (TEM).
- Quantification of phage infectivity using plaque assays and TEM-based structural damage assessment.
Main Results:
- Jet nebulization caused significant structural damage and infectivity loss in Myoviridae (PEV40) and Siphoviridae (D29) phages.
- Podoviridae (PEV2) showed negligible changes in activity and structure after nebulization.
- TEM underestimated titer reduction for Siphoviridae (D29), highlighting the severity of damage.
- Phage deactivation correlated with morphological damage, particularly tail length.
Conclusions:
- Nebulization-induced loss of phage infectivity is linked to morphological damage.
- Phage tail length is a critical factor in determining susceptibility to jet nebulization.
- Siphoviridae and Myoviridae phages may be less suitable for inhaled therapy using jet nebulization compared to Podoviridae due to structural fragility.
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