Use of lineage specific bacteriophage to counter antibiotic resistant Escherichia coli sequence type 131 (ST131)

Abstract

The emergence and rapid dissemination of multidrug resistant pathogens presents a huge and growing global concern. Escherichia coli (E. coli) sequence type (ST) 131, has been recognised as a major E. coli lineage responsible for the spread of multidrug resistance, and is a common cause of life-threatening infections in clinical settings. In recent years there has been increasing interest in the use of bacteriophages in the treatment of MDR infections. The use of bacteriophages with some breadth of host range can be desirable so that licensed products are able to target a range of clinical infections. Using a unique method of quantifying host range, we provide evidence that the type of environment sampled from, and the host strain used for isolation are both significant determinants of the host range of phages isolated. Using competition experiments we also provide evidence that by combining the selective pressure of phage predation with that imposed by the presence of a probiotic competitor, significant reductions in the fitness of the MDR pathogen ST131, can be achieved. Although fitness trade-offs resulting from bacteriophage resistance are predicted by life-history evolution, we demonstrate that resistant mutants do not pay a cost for resistance but instead appear to benefit from it with the relative fitness of resistant mutants greater than their susceptible counterparts. Overall, this study draws attention to the value of the environment as a source of naturally occurring antimicrobials, provides direction for future sampling attempts to promote the isolation of phage with the greatest therapeutic potential and demonstrates how the efficacy of such phage can be enhanced through their synergistic application with probiotic strains such as E. coli Nissle 1917. This study and those that follow will provide invaluable contributions to the ever-growing body of phage research that will ultimately form part of the solution in the fight against AMR.