Phages against MDR Enterococcus faecium

ended

Due to its multidrug resistance (MDR), Enterococcus faecium (Efm) poses a challenge to the healthcare system and renders most standard antibiotics useless. Bacteriophage (phage) therapy has resurfaced as a treatment strategy for bacterial infections due to increasing antibiotic resistance. Its advantages include specificity, low side effects and production costs, especially when used in combination with standard-of-care antibiotics. Phage therapy has been successful in compassionate use, but its wider implementation is hindered by a lack of knowledge on which antibiotics phages synergize and the mechanisms behind remain elusive. Our project is unique in that it aims to enable the use of conventional antibiotics in MDR Efm through phages. We want to explore which antibiotic classes phages synergize with, which survival strategies Efm uses against phages, and how host factors influence the ability of the antibiotic-phage combination to kill Efm. First, we will investigate phages' interaction with different antibiotic classes against Efm. We will explore the dynamics of phage-antibiotic combinations and whether they are additive, synergistic, or antagonistic. Second, potential phage survival strategies of Efm will be investigated. Additionally, membrane vesicles will be investigated as a potential survival strategy against phages, and their ability to act as a decoy and protect the bacterium from phages will be studied. Third, we will investigate the impact of host factors on the phage-antibiotic killing of Efm, to see whether they can enhance or suppress the phage-antibiotic killing. This approach will provide a deeper understanding of the phages-antibiotic interaction against MDR Efm strains, as well as potential survival systems of Efm which may also shed light on possible mitigation strategies. Overall, this approach has the potential to enable the use of standard-of-care drugs against MDR bacterial infections in general.