Functional genomic characterization of anti-phage defense systems in vancomycin-resistant Enterococcus faecium

Vancomycin-resistant Enterococcus faecium (VREfm) poses a major public health concern due to its high antibiotic resistance and frequent hospital-acquired infections. Phages present a promising alternative therapy to control bacterial populations and manage VREfm infections. However, the anti-phage defense systems present in VREfm have not been extensively studied.

In this study, researchers analyzed the genomes of 21 clinical VREfm isolates, using DefenseFinder and PADLOC tools to identify potential anti-phage defense systems. They discovered that most of these systems were located on plasmids, defense islands, and prophages. After testing the phage susceptibility of these isolates, no clear link was found between specific defense systems and resistance to four phages targeting VREfm.

To overcome the limitations of phage susceptibility testing, the researchers developed an assay to evaluate phage survival after co-incubation with bacteria. This approach led to the identification of over two dozen genes associated with phage killing, including a potentially novel defense island. The researchers also attempted to validate 10 candidate anti-phage defense systems, but only four of them were tested in enterococci.

Expression of one candidate, AbiE, was found to reduce bacterial susceptibility to two phages targeting Enterococcus. As phage therapy becomes more widespread in treating VREfm, identifying genes responsible for phage resistance can help optimize the delivery of phages to patients who may benefit from this innovative treatment.