addressing risk factors may lead to broader use of phage therapeutics

ADDRESSING RISK FACTORS MAY LEAD TO BROADER USE OF PHAGE THERAPEUTICS
GLONTI, Tea 1, PIRNAY, Jean-Paul 1
1Laboratory for Molecular and Cellular Technology, Queen Astrid Military Hospital, Brussels, Belgium
[email protected]
Introduction: With the collapse of the antibiotic market, there is an undeniable need to develop new therapeutic antibacterials, and this is precisely the reason for the growing interest in bacteriophages. To make progress in the development of therapeutics, it is necessary to consider properly designed and standardized procedures of development and handling at all levels, including proper interpretation/evaluation of phage/cocktail activity in vitro against bacterial mono- or co-cultures, using of a high diversity of phage/bacteria assemblages. Here we propose a predictive outline of a procedure for effective and rapid evaluation and selection of candidate phages; and criteria (risk factors) that should be considered when designing and producing phage cocktails.
Material & Methods:
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Evaluation-based selection of P. aeruginosa and K. pneumoniae candidate phages, considering risk factors such as phage or bacteria inhibition in phage/phage, phage/bacteria and bacteria/bacteria co-proliferation.
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Evaluation-based differentiation between rapid (initial) and time-consuming methods used at different stages of the phage efficacy study.
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Determine of the mode of action (synergy, proto-cooperation or antagonism) of phages in cocktails or in combination with antibiotics using the developed “interpretation model” (using a total of 257 strains for both species).
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Development and upload of approved and ready-to-use phage cocktail formulations (recipes).
Results and discussions: Fourteen P. aeruginosa and K. pneumoniae phage cocktails were developed and tested on large panels of bacteria-kits with different genetic backgrounds/virulence factors, source of isolation and geographic origin. The phage bi- and tri-cocktails suppress the growth of phage-resistant mutants and overcome the inhibitory effect in vitro, resulting in synergy or proto-cooperation. Using an evaluation-based approach and developing a large set of ready-to-use phage cocktail formulations is an incredibly efficient way to interactively and rapidly evaluate and select the right phage candidates and predict their treatment potential.