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新型多样性生成机制在耐碳青霉烯鲍曼不动杆菌抗性岛上由 Tn7 样元件驱动。

Novel mechanisms of diversity generation in Acinetobacter baumannii resistance islands driven by Tn7-like elements.

机构信息

Department of Microbiology, Cornell University, Ithaca, NY, USA.

College of Life Sciences and Engineering Research Center of Bioreactor and Pharmaceutical Development (Ministry of Education), Jilin Agricultural University, Changchun City, Jilin Province, China.

出版信息

Nucleic Acids Res. 2024 Apr 12;52(6):3180-3198. doi: 10.1093/nar/gkae129.

Abstract

Mobile genetic elements play an important role in the acquisition of antibiotic and biocide resistance, especially through the formation of resistance islands in bacterial chromosomes. We analyzed the contribution of Tn7-like transposons to island formation and diversification in the nosocomial pathogen Acinetobacter baumannii and identified four separate families that recognize different integration sites. One integration site is within the comM gene and coincides with the previously described Tn6022 elements suggested to account for the AbaR resistance island. We established Tn6022 in a heterologous E. coli host and confirmed basic features of transposition into the comM attachment site and the use of a novel transposition protein. By analyzing population features within Tn6022 elements we identified two potential novel transposon-encoded diversification mechanisms with this dynamic genetic island. The activities of these diversification features were confirmed in E. coli. One was a novel natural gain-of-activity allele that could function to broaden transposition targeting. The second was a transposon-encoded hybrid dif-like site that parasitizes the host dimer chromosome resolution system to function with its own tyrosine recombinase. This work establishes a highly active Tn7-like transposon that harnesses novel features allowing the spread and diversification of genetic islands in pathogenic bacteria.

摘要

移动遗传元件在抗生素和杀生物剂耐药性的获得中起着重要作用,特别是通过在细菌染色体中形成耐药岛。我们分析了 Tn7 样转座子对医院病原体鲍曼不动杆菌中岛形成和多样化的贡献,并确定了四个识别不同整合位点的独立家族。一个整合位点位于 comM 基因内,与先前描述的 Tn6022 元素重合,该元素被认为是 AbaR 耐药岛的原因。我们在异源大肠杆菌宿主中建立了 Tn6022,并证实了转座到 comM 附着位点的基本特征以及使用新型转位蛋白。通过分析 Tn6022 元件内的群体特征,我们确定了这种动态遗传岛中两个潜在的新转座子编码多样化机制。这些多样化特征的活性在大肠杆菌中得到了证实。一种是新型的天然获得活性等位基因,可用于拓宽转位靶向。第二种是转座子编码的混合 dif 样位点,它寄生在宿主二聚体染色体分辨率系统中,与自身的酪氨酸重组酶一起发挥作用。这项工作建立了一个高度活跃的 Tn7 样转座子,利用新的特性允许在致病菌中传播和多样化遗传岛。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a26/11014353/95b176d2ce8f/gkae129figgra1.jpg

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