Biomorphological and related technical aspects affecting phage activity for inhaled application

Autor: Claudius Seitz, Markus C. Brack, Sarah Wienecke, Sandra-Maria Wienhold, Holger Ziehr, Manfred Rohde, Imke H. E. Korf, Wibke Groenewald, Antonia Dannheim, Martin Witzenrath, Christine Rohde, Geraldine Nouailles
Rok vydání: 2020
Předmět:
Zdroj: Respiratory infections.
Popis: Introduction: In 2014, the WHO proclaimed the beginning of a post-antibiotic era [1]. As alternatives to antibiotics, bacteriophages are increasingly coming into focus to combat the increasing number of resistant bacteria. In order to reach infected sites in the lungs and reduce unwanted systemic effects, nebulization of drugs is a favorable way of application. The infectivity of phages with different tail lengths after nebulization was tested under various conditions. This project is part of Phage4Cure, a BMBF-funded study examining the use of phages against lung infections. Methods: Long-tailed (Siphoviridae), short-tailed (Podoviridae) and medium long tailed (Myoviridae) phages from the order Caudovirales were analyzed. Four different phages per morphotype were nebulized with a JET nebulizer. Additionally, three phages (two Myoviridae, one Podovirus) were purified according to laboratory standards. By using the double-agar overlay method, titers after nebulization were compared to the stock solution. Results: Phages of the type Siphoviridae showed the highest titer losses during nebulization and Podoviridae the lowest. Among the Myoviridae variable and phage-dependent titer loss was observed. In the mesh nebulization system, all three phages showed a loss of titer after nebulization independent of the purification degree. Only one of the purified phages showed a higher titer loss after nebulization compared to lysate. Conclusion: For successful phage inhalation therapy, the effects of nebulizer technology, the size of the phage tail and purity must be considered. [1] www.who.int/mediacentre/news/releases/2014/amr-report/en/
Databáze: OpenAIRE