Molecular mechanisms of enterococcal-bacteriophage interactions and implications for human health

Once overlooked as passive bystanders of the human intestinal microbiota, new evidence is shedding light on the importance of enterococci and their bacteriophages (phages) in shaping human health. Natural predators of enterococci, phages represent a narrow spectrum, precision targeting modality for the eradication of problematic enterococci within the microbiota or infected tissue. The identification of enterococcal phage receptors, absorption factors, and transcriptional responses following phage infection reveals a complex predator-prey relationship that modulates enterococcal cell surface architecture, susceptibility to antibiotics, and adaptation to host associated environments. Considering the dry up of contemporary antibiotic discovery pipelines in the pharmaceutical industry and a continued emergence of multidrug-resistant enterococci, enterococcal phages may serve as bonafide therapeutics. We highlight current advances in enterococcal phage biology with emphasis on recent breakthroughs in potential therapeutic applications that place enterococcal phages at the forefront of next-generation biologics.