Invertible promoters mediate bacterial phase variation, antibiotic resistance, and host adaptation in the gut.

Science
Authors
Abstract

Phase variation, the reversible alternation between genetic states, enables infection by pathogens and colonization by commensals. However, the diversity of phase variation remains underexplored. We developed the PhaseFinder algorithm to quantify DNA inversion-mediated phase variation. A systematic search of 54,875 bacterial genomes identified 4686 intergenic invertible DNA regions (invertons), revealing an enrichment in host-associated bacteria. Invertons containing promoters often regulate extracellular products, underscoring the importance of surface diversity for gut colonization. We found invertons containing promoters regulating antibiotic resistance genes that shift to the ON orientation after antibiotic treatment in human metagenomic data and in vitro, thereby mitigating the cost of antibiotic resistance. We observed that the orientations of some invertons diverge after fecal microbiota transplant, potentially as a result of individual-specific selective forces.

Year of Publication
2019
Journal
Science
Volume
363
Issue
6423
Pages
181-187
Date Published
2019 01 11
ISSN
1095-9203
DOI
10.1126/science.aau5238
PubMed ID
30630933
Links
Grant list
P30 DK043351 / DK / NIDDK NIH HHS / United States
R01 AT009708 / AT / NCCIH NIH HHS / United States