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可逆启动子介导肠道中的细菌相变异,抗生素抗性和宿主适应

发布者:抗性基因网 时间:2019-01-14 浏览量:1320

摘要

相变,遗传状态之间的可逆交替,使病原体感染和共生殖民化。 然而,相位变化的多样性仍未得到充分研究。 我们开发了PhaseFinder算法来量化DNA反转介导的相位变化。 系统搜索了5475个细菌基因组,确定了4686个基因间可逆DNA区域(反转子),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,强调表面多样性对肠道定植的重要性。 我们发现含有调节抗生素抗性基因的启动子的逆转子在人体宏基因组数据和体外抗生素处理后转变为ON方向,从而降低了抗生素抗性的成本。 我们观察到一些逆转子的取向在粪便微生物群移植后发生分歧,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.


https://www.ncbi.nlm.nih.gov/pubmed/30630933