Bacteriophages (phages) are being considered as alternative
therapeutics for the treatment of multidrug resistant
bacterial infections. Considering phages have narrow host-ranges, it is generally accepted that therapeutic phages will have a marginal impact on non-target bacteria. We have discovered that lytic phage
infection induces transcription of type VIIb
secretion system (T7SS) genes in the pathobiont Enterococcus faecalis. Membrane damage during phage
infection induces T7SS gene expression resulting in cell contact dependent antagonism of different Gram positive bystander bacteria. Deletion of essB, a T7SS structural component, abrogates phage-mediated killing of bystanders. A predicted immunity gene confers protection against T7SS mediated inhibition, and disruption of its upstream LXG toxin gene rescues growth of E. faecalis and Staphylococcus aureus bystanders. Phage induction of T7SS gene expression and bystander inhibition requires IreK, a
serine/threonine kinase, and OG1RF_11099, a predicted GntR-family
transcription factor. Additionally, sub-lethal doses of membrane targeting and
DNA damaging
antibiotics activated T7SS expression independent of phage
infection, triggering T7SS antibacterial activity against bystander bacteria. Our findings highlight how phage
infection and
antibiotic exposure of a target bacterium can affect non-target bystander bacteria and implies that
therapies beyond
antibiotics, such as
phage therapy, could impose collateral damage to polymicrobial communities.