Abstract
Phage therapy, treating bacterial infections with bacteriophages, could be a future alternative to antibiotic treatment of bacterial infections. There are, however, several problems to be solved, mainly associated to the biology of phages, the interaction between phages and their bacterial hosts, but also to the vast variation of pathogenic bacteria which implies that large numbers of different phages are going to be needed. All of these phages must under present regulation of medical products undergo extensive clinical testing before they can be applied. It will consequently be of great economic importance that effective and versatile phages are selected and collected into phage libraries, i.e., the selection must be carried out in a way that it results in highly virulent phages with broad host ranges. We have isolated phages using the Escherichia coli reference (ECOR) collection and compared two methods, spot testing and efficiency of plating (EOP), which are frequently used to identify phages suitable for phage therapy. The analyses of the differences between the two methods show that spot tests often overestimate both the overall virulence and the host range and that the results are not correlated to the results of EOP assays. The conclusion is that single dilution spot tests cannot be used for identification and selection of phages to a phage library and should be replaced by EOP assays. The difference between the two methods can be caused by many factors. We have analysed if the differences and lack of correlation could be caused by lysis from without, bacteriocins in the phage lysate, or by the presence of prophages harbouring genes coding for phage resistance systems in the genomes of the bacteria in the ECOR collection.
Highlights
Phage therapy involves clinical treatment of bacterial infections with phages
There is an excess of phages to be found against every bacterial strain but only highly virulent phages with a broad host range will be selected
High virulence depends on the burst size of a phage, which is a prerequisite for reaching productive infection which in turn is of key importance for successful treatment
Summary
Phage therapy involves clinical treatment of bacterial infections with phages (bacteriophages). The large variation of increasingly multiresistant bacteria causing infections will demand a large number of different and wellcharacterised phages that all have been approved for clinical treatment. This can be accomplished by the establishment of phage libraries consisting of phages that all have passed clinical trials. When establishing a phage library, it is highly desirable that collected phages show high virulence on a large number of bacterial strains. A high burst size increases the probability that phages reach target bacteria, which is crucial for achieving a productive infection, and reaching the benefits that phages have compared with antibiotics [9]. If phages can eliminate infecting bacteria faster than they can replicate, a high burst size results in a lower risk of selection for phage resistant bacteria [9]
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