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

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Science  11 Jan 2019:
Vol. 363, Issue 6423, pp. 181-187
DOI: 10.1126/science.aau5238

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Switching ON resistance

Clonal bacterial colonies will often grow dissimilar patches, similar to a tortoiseshell pattern. These differing phenotypes arise by reversible mechanisms called phase variation. Jiang et al. developed an algorithm to survey bacterial genomes for invertible promoters that cause phase variation. Inverted repeats signal the presence of these promoters, which can flip between ON and OFF states catalyzed by phage integrase analogs called invertases. Invertible promoters linked to antibiotic resistance genes were widespread among vertebrate gut–associated organisms, including Bacteroidetes, Spirochaetes, and Verrucomicrobia. These bacteria are thus equipped and prepared for sudden environmental stress, including antibiotic exposure.

Science, this issue p. 181


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.

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