Abstract
Bacteriophage predation has selected for widespread and diverse anti-phage systems that frequently cluster on mobilizable defense islands in bacterial genomes. Understanding phage-host co-evolutionary dynamics has lagged due to a dearth longitudinal sampling in natural environments. Here, using time shift experiments we show that epidemic Vibrio cholerae and lytic phages recovered from cholera patient stool samples display negative frequency-dependent co-evolution. We find that SXT integrative and conjugative elements (ICEs), which are infamous for conferring antibiotic resistance, invariably encode phage defense systems. SXT ICEs in V. cholerae govern susceptibility to phages in clinical samples and we demonstrate phage counter-adaptation to SXT ICE restriction over a three-year sampling period. Further, phage infection stimulates high frequency SXT ICE conjugation, leading to the concurrent dissemination of phage and antibiotic resistance.
Competing Interest Statement
K.D.S. is a scientific advisor for Nextbiotics, Inc.