Jet nebulization of bacteriophages with different tail morphologies – Structural effects

Jet nebulization of bacteriophages with different tail morphologies – Structural effects.

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Item Type: Article
Status: Published
Official URL:
Journal or Publication Title: International Journal of Pharmaceutics
Volume: 554
Page Range: pp. 322-326
Date: 2019
Divisions: Tuberculosis
Depositing User: General Admin
Identification Number: 10.1016/j.ijpharm.2018.11.026
ISSN: 03785173
Date Deposited: 15 Dec 2020 01:00

It 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) andSiphoviridae (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.

Keywords: Cryo-TEM; Drug-resistance; Nebulizer; Phage; Pulmonary infections.

Copyright © 2018. Published by Elsevier B.V.

Leung, Sharon Shui Yee
Carrigy, Nicholas B.
Vehring, Reinhard
Finlay, Warren H.
Morales, Sandra
Carter, Elizabeth A.
Britton, Warwick J.
Kutter, Elizabeth
Chan, Hak-Kim
Last Modified: 15 Dec 2020 01:00

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