Temporal shifts in antibiotic resistance elements govern phage-pathogen conflicts

Area of Science:

• Microbiology
• Genomics
• Evolutionary Biology

Background:

• Bacteriophage predation drives bacterial evolution of antiphage systems.
• These systems often cluster on mobilizable defense islands in bacterial genomes.
• Understanding phage-bacterial coevolution is crucial for phage therapy and pathogen evolution insights.

Purpose of the Study:

• Investigate phage-bacterial adaptation dynamics in clinical Vibrio cholerae.
• Map phage resistance determinants to mobile genetic elements.
• Identify mechanisms of phage counter-adaptation and bacterial defense.

Main Methods:

• Time-shift experiments with clinical Vibrio cholerae samples.
• Mapping phage resistance genes to SXT integrative and conjugative elements (ICEs).
• Identifying phage-encoded defense inhibitors and mechanisms of phage resistance.

Main Results:

• Observed fluctuations in Vibrio cholerae phage resistance in clinical samples.
• Identified SXT ICEs as key carriers of phage resistance determinants.
• Documented phage counter-defense mechanisms and a novel phage-encoded defense inhibitor.
• Phage infection induced high-frequency SXT ICE conjugation, spreading phage and antibiotic resistance.

Conclusions:

• SXT ICEs are central to phage-bacterial coevolution, mediating both defense and resistance dissemination.
• Phages can overcome bacterial defenses and even select for novel phage-encoded inhibitors.
• Phage-host interactions drive the concurrent spread of phage and antibiotic resistance in clinical settings.