Pneumologie 2020; 74(S 01): 21
DOI: 10.1055/s-0039-3403107
Posterbegehung (PO02) – Sektion Zellbiologie
Neue Innovationen in der Zellbiologie
Georg Thieme Verlag KG Stuttgart · New York

Impact of phage morphologies on titer reduction due to nebulization – a blueprint for clinical application

SM Wienhold
1   Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Infectious Diseases and Respiratory Medicine and Division of Pulmonary Inflammation, Berlin
,
MC Brack
1   Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Infectious Diseases and Respiratory Medicine and Division of Pulmonary Inflammation, Berlin
,
W Groenewald
1   Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Infectious Diseases and Respiratory Medicine and Division of Pulmonary Inflammation, Berlin
,
G Nouailles
1   Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Infectious Diseases and Respiratory Medicine and Division of Pulmonary Inflammation, Berlin
,
I Korf
2   Leibniz Institute Dsmz – German Collection of Microorganisms and Cell Cultures, Braunschweig
,
M Rohde
3   Helmholtz Centre for Infection Research, Central Facility for Microscopy, Braunschweig
,
C Seitz
4   Fraunhofer Institute for Toxicology and Experimental Medicine (Item), Department of Pharmaceutical Biotechnology, Braunschweig
,
A Dannheim
4   Fraunhofer Institute for Toxicology and Experimental Medicine (Item), Department of Pharmaceutical Biotechnology, Braunschweig
,
S Wienecke
4   Fraunhofer Institute for Toxicology and Experimental Medicine (Item), Department of Pharmaceutical Biotechnology, Braunschweig
,
H Ziehr
4   Fraunhofer Institute for Toxicology and Experimental Medicine (Item), Department of Pharmaceutical Biotechnology, Braunschweig
,
C Rohde
2   Leibniz Institute Dsmz – German Collection of Microorganisms and Cell Cultures, Braunschweig
,
M Witzenrath
1   Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Infectious Diseases and Respiratory Medicine and Division of Pulmonary Inflammation, Berlin
› Author Affiliations
Further Information

Publication History

Publication Date:
28 February 2020 (online)

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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.