10.6078/D1GT5S
LeGault, Kristen
0000-0002-9896-6983
University of California, Berkeley
Temporal shifts in antibiotic resistance elements govern phage-pathogen
conflicts
Dryad
dataset
2021
Microbiology, evolution, bacteriophages
2021-05-21T00:00:00Z
2021-05-21T00:00:00Z
en
https://doi.org/10.1101/2020.12.16.423150
29544 bytes
4
CC0 1.0 Universal (CC0 1.0) Public Domain Dedication
Bacteriophage predation selects for diverse anti-phage systems that
frequently cluster on mobilizable defense islands in bacterial genomes.
However, there remains a lack of molecular insight into the reciprocal
dynamics of phage-bacterial adaptations in nature, particularly in
clinical contexts where there is need to inform phage therapy efforts and
understand how phages drive pathogen evolution. Here, we used time-shift
assays to evaluate whether clinical Vibrio cholerae isolates were
susceptible to infection by phage from past, future or contemporaneous
patient samples. Across a 34-month sampling period, we discover that phage
resistance is governed by fluctuations in SXT integrative and conjugative
elements (ICEs), which notoriously also confer antibiotic resistance. We
further demonstrate potential trade-offs for having SXT ICEs, as we show
they can also can restrict beneficial mobile genetic elements. We discover
phage counter-adaptation to SXT-mediated restriction in clinical samples,
and show that flux of SXT ICEs in V. cholerae over time allows for
re-emergence of phage resistance. We find that SXT ICEs, which are
widespread in Gammaproteobacteria, invariably encode phage defense and
function to protect other genera from phage attack following conjugation.
Further, we find that phage infection stimulates high frequency SXT ICE
conjugation, leading to the concurrent dissemination of phage and
antibiotic resistance.
WYL-domain proteins and the downstream flanking gene encoding the
conjugative relaxase TraI were extracted from all identifiable hotspot
5's encoded by SXT ICEs. MUSCLE alignments were performed on the
nucleotide sequence for each unique gene, and a phylogenetic tree was
constructed using PhyML with 100 bootstrap iteractions. Phylogenetic trees
were visualized in FigTree v1.4.4.
The unique genes sequences for each WYL-domain protein are uploaded as an
Excel spreasheet. The datasheet indicates which WYL-domain protein
encoding genes are identical between SXT ICEs, and the tree was only
constructed using one of the unique WYL-domain proteins. Of note: The tree
displays the WYL-domain protein encoding gene for ICEVchCHN1605, yet the
published manuscript is showing this node labelled ICEVchCHN956. These two
WYL-domain protein containing genes are identical, and these two SXT ICEs
are so similar that the cut-offs for our BLASTn analysis identified them
as the same SXT ICE. The trees are uploaded in the NEWICK file format.