Invertible promoters mediate bacterial phase variation, antibiotic resistance, and host adaptation in the gut
Invertible promoters mediate bacterial phase variation, antibiotic resistance, and host adaptation in the gut
复制标题
DOI：
10.1126/science.aau5238
复制
发表时间：
2019-01-11
期刊：
影响因子：
56.9
通讯作者：
Xavier, Ramnik J.
中科院分区：
文献类型：
--
作者：
Jiang, Xiaofang;Hall, A. Brantley;Xavier, Ramnik J.
阶段变化，遗传状态之间的可逆交替，使病原体感染和寄生虫定植成为可能。然而，相位变化的多样性仍有待探索。我们开发了Phasephase算法来量化DNA倒位介导的相位变化。对54，875个细菌基因组的系统搜索确定了4686个基因间可逆DNA区域（invertons），揭示了宿主相关细菌的富集。含有启动子的Invertons通常调节细胞外产物，强调了表面多样性对肠道定植的重要性。我们在人类宏基因组数据和体外发现了含有调节抗生素耐药基因的启动子的倒置子，这些基因在抗生素治疗后转向ON方向，从而减轻了抗生素耐药性的成本。我们观察到，粪便微生物群移植后，一些倒置分子的方向发生了变化，这可能是个体特异性选择力的结果。
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.