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DOI: 10.1055/s-0039-3403107
Impact of phage morphologies on titer reduction due to nebulization – a blueprint for clinical application
Publikationsverlauf
Publikationsdatum:
28. Februar 2020 (online)
Introduction: Antimicrobial resistance constitutes one of the major public health concerns. Pseudomonas aeruginosa (P. aeruginosa) causes mainly respiratory infections and is one of the most prevalent multidrug resistant bacteria. Bacteriophages are viruses, which are natural predators of bacteria and are highly specific for their host strain without affecting other bacterial species. However, local application is preferred to ensure contact with bacterial cells. Nebulization is a very effective way to transport pharmaceuticals into the lung and is a favourable method for treatment of airway infections. Therefore, the impact of different aerosolization systems on phage morphologies and their ability to reduce bacterial counts was tested. This investigation is embedded in Phage4Cure, a BMBF funded study aiming to use phages against P. aeruginosa lung infections.
Methods: Twelve phages from the order Caudovirales with different tail lengths were aerosolized with JET-nebulizer. Titers before and after aerosolization were compared using double-agar overlay method. Three highly potent phages were then chosen and purified according to GLP standards and aerosolized via Mesh-nebulizer. In addition to determination of titers before and after aerosolization, the effects of phage purification on titer loss was assessed.
Results: JET nebulization resulted in highly significant titer reduction for long-tailed phages (Siphoviridae) whereas short-tailed phages (Podoviridae) showed no significant titer loss. Phages with medium long tails (Myoviridae) displayed variable titer loss. Nebulization of phages with a vibrating mesh system resulted in loss of titer in all three phages irrespective of the purification degree. Only one purified phage (Myoviridae) showed a significantly higher titer loss compared to nebulization of crude lysate.
Conclusion: Morphologies of phages as well as the degree of purification can influence titer loss due to nebulization and should be considered when selecting phages for inhaled application.