Jet nebulization of bacteriophages with different tail morphologies – Structural effects
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AbstractIt was previously demonstrated that the loss of infectivity of a myovirus PEV44 after jet nebulization was closely related to a change in bacteriophage (phage) structure. In this follow-up study, we further examined the impact of jet nebulization on tailed phages, which constitute 96% of all known phages, from three different families, Podoviridae (PEV2), Myoviridae (PEV40) and Siphoviridae (D29). Transmission electron microscopy (TEM) identified major changes in phage structures after jet nebulization, correlating with their loss of infectivity. For the podovirus PEV2, jet nebulization had a negligible impact on its activity (0.04 log10 pfu/mL loss) and structural change. On the other hand, the proportion of intact phages in the nebulized samples dropped from 50% to ∼27% for PEV40 and from 15% to ∼2% for D29. Phage deactivation of PEV40 measured by the TEM structural damage (0.52 log10 pfu/mL) was lower than that obtained by plaque assay (1.02 log10 pfu/mL), but within the range of variation (±0.5 log10 pfu/mL). However, TEM quantification considerably underestimated the titer reduction of D29 phage, ∼2 log pfu/mL lower than that obtained in plaque assay (3.25 log10 pfu/mL loss). In conclusion, nebulization-induced titre loss was correlated with morphological damage to phages and in particular, the tail length may be an important consideration for selection of phages in inhaled therapy using jet nebulization.
Acceptance Date11/11/2018
All Author(s) ListSharon Shui Yee Leung, Nicholas B. Carrigy, Reinhard Vehring, Warren H. Finlay, Sandra Morales, Elizabeth A. Carter, Warwick J. Britton, Elizabeth Kutter, Hak-Kim Chan
Journal nameInternational Journal of Pharmaceutics
Year2019
Month1
Day13
Volume Number554
Pages322 - 326
ISSN0378-5173
eISSN1873-3476
LanguagesEnglish-United States
KeywordsPhage, Nebulizer, Cryo-TEM, Drug-resistance, Pulmonary infections

Last updated on 2020-04-04 at 12:20