PT  - JOURNAL ARTICLE
AU  - Anushila Chatterjee
AU  - Julia L. E. Willett
AU  - Gary M. Dunny
AU  - Breck A. Duerkop
TI  - Phage infection mediates inhibition of bystander bacteria
AID  - 10.1101/2020.05.11.077669
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.05.11.077669
4099  - http://biorxiv.org/content/early/2020/05/11/2020.05.11.077669.short
4100  - http://biorxiv.org/content/early/2020/05/11/2020.05.11.077669.full
AB  - Bacteriophages (phages) are being considered as potential alternative therapeutics for the treatment of multidrug resistant bacterial infections. Considering most phages have a narrow host-range, the generally accepted dogma is that therapeutic phages will have a marginal impact on bacterial strains outside of their intended target bacterium. We have discovered that lytic phage infection induces transcription of type VIIb secretion system (T7SS) genes in the pathobiont Enterococcus faecalis. Phage induction of T7SS genes mediates cell contact dependent antagonism of diverse Gram positive bystander bacteria. This phage induced T7SS antagonism is attributed to cell membrane damage. Phage driven T7SS antagonism of neighboring cells is abrogated by deleting essB, a T7SS structural component that is required for secretion of T7SS toxic substrates. Expression of a predicted immunity gene in bystander bacteria confers protection against T7SS mediated inhibition, implicating an upstream LXG domain toxin in intraspecies antagonism. Additionally, phage induction of T7SS gene expression requires IreK, a Serine/Threonine PASTA kinase. Phage induction of T7SS antimicrobial activity signals through a non-canonical IreK stress response pathway. Our findings highlight how phage infection of a target bacterium can unintentionally affect neighboring bystander bacteria. Furthermore, our work indicates that before phages become a standard of care in the clinic, we must clearly understand how bacteria respond to phage infection and what, if any, collateral effects phage therapy may have on non-target bacteria, such as the microbiota.Competing Interest StatementThe authors have declared no competing interest.