At Leibniz-Institut DSMZ GmbH, phage screening was successfully completed. Since the beginning of the project, it has been the basis for all subsequent steps of the project and has led to a selection of promising phage species, which in combination show a comparatively high bacterial host coverage of Pseudomonas aeruginosa strains.
Detailed investigation of many different phages with regard to their efficiency in destroying the host bacteria and many other aspects finally narrowed the circle of possible candidates for further processing by ITEM. Basically, it was desired that the phages would complement each other significantly in their bacterial coverage in order to increase the final coverage percentage of patient strains in the clinical application. On the other hand, it was desired that the phages overlap in their bacterial coverage so that more than one phage can effectively attack patient strains as often as possible.
Such forward-looking considerations and, in addition, the greatest possible genetic and morphological diversity of phage contribute significantly to the efficiency of the final phage product and are based on the biology of the individual phage. Therefore, phages for clinical application must be comprehensively investigated and compared, always with the aim of successful high purification. Consequently, they must also produce high titres, be stable in the event of slight temperature or pH fluctuations, remain stable in the planned application form, etc.
The fact that these factors are present in many phages is due to the fortunate circumstance of evolution: Phages are the most common living units on earth, ensure the continuous turnover of one third of the global bacterial mass and live as a regulatory force in our own microbiome. In the meantime, three different phages have been selected as candidates and were handed over to ITEM for reproduction.
During the further course of the project, Leibniz Institute DSMZ GmbH will continue to work on the characterisation of these phages in order to learn more about the three phages with regard to their effectiveness as phage “cocktails” in comparison to the effect of antibiotics or about their effectiveness in artificial biofilms or artificial sputum medium.
Immediately after receipt of the phages, the multi-stage, complex sequence of production steps for the propagation and purification of these three candidates began at the Fraunhofer Institute ITEM. At the moment, the research group is trying to optimize the purification process.
At a recent meeting of the project participants in Berlin, the toxicological programme of the pre-clinic was coordinated. The aim is to ensure that, as far as possible, future project phases are harmonised between the partners at an early stage and adapted to regulatory requirements, so that the preclinical development work can be tackled in a timely manner as soon as phage material is available from ITEM.