Phage infection and sub-lethal antibiotic exposure mediate Enterococcus faecalis type VII secretion system dependent...

Area of Science:

• Microbiology
• Bacteriology
• Molecular Biology

Background:

• Bacteriophages (phages) are explored as alternatives to antibiotics for multidrug-resistant infections.
• Phages are typically assumed to have minimal impact on non-target bacteria due to their narrow host ranges.
• The potential for collateral damage to microbial communities by phage therapy is not well understood.

Purpose of the Study:

• To investigate the impact of lytic phage infection on non-target bacteria.
• To determine the mechanisms by which phages affect bystander bacteria.
• To explore if other treatments, like antibiotics, can induce similar effects.

Main Methods:

• Lytic phage infection of Enterococcus faecalis.
• Gene expression analysis of type VIIb secretion system (T7SS) genes.
• Deletion mutagenesis of T7SS components (essB) and regulatory genes (IreK, OG1RF_11099).
• Assays for bystander bacterial killing and protection mechanisms.
• Exposure to sub-lethal antibiotic doses.

Main Results:

• Phage infection induces T7SS gene expression in E. faecalis.
• Induced T7SS mediates contact-dependent killing of Gram-positive bystander bacteria.
• Deletion of T7SS genes or disruption of toxin/immunity genes abrogates bystander killing.
• Phage-induced T7SS activation requires specific kinases and transcription factors.
• Antibiotics also activate T7SS and bystander killing.

Conclusions:

• Phage infection can lead to collateral damage to bystander bacteria via T7SS activation.
• This mechanism highlights potential unintended consequences of phage therapy in polymicrobial environments.
• Antibiotic exposure can also trigger T7SS-mediated collateral damage, suggesting broader implications for microbial community disruption.